When emulsification meets self-assembly: The role of emulsification in directing block copolymer assembly

Progress in Polymer Science 36 (2011) 1152–1183

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Progress in Polymer Science journal homepage: www.elsevier.com/locate/ppolysci

When emulsification meets self-assembly: The role of emulsification in directing block copolymer assembly Ian Wyman, Gabriel Njikang, Guojun Liu ∗ Department of Chemistry, Queen’s University, 90 Bader Lane, Kingston, Ontario, Canada K7L 3N6

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Article history: Received 31 January 2011 Received in revised form 26 April 2011 Accepted 27 April 2011 Available online 26 May 2011 Keywords: Directed assembly Emulsification Block copolymers Confinement effects Self-assembly Double emulsions Emulsification/solvent evaporation

a b s t r a c t Emulsification is used to generate spherical particles or droplets of immiscible liquids, while block copolymer self-assembly yields a wide variety of nanostructures. The combination of these two methodologies can yield a variety of structures that would not be otherwise observed. The emulsification/solvent evaporation process provides a powerful means to direct block copolymer assembly. Various factors arising from the emulsification can direct the block copolymer assembly, such as confinement effects, interfacial tension, as well as other conditions. In this review, various emulsification techniques are discussed, such as oil-in-water emulsions, double emulsions, as well as the use of microfluidic devices. While emulsification-induced self-assembly may be used to control internal morphologies as well as overall shapes of particles, it also lends a convenient method for controlling surface structures. Examples of exotic structures that may be obtained through the use of these techniques will be described. Also, ways in which morphologies may be controlled using these methods will be discussed. © 2011 Elsevier Ltd. All rights reserved.

Contents 1. 2.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1153 Block copolymer self-assembly in confined volumes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1155 2.1. Computer simulation results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1155 2.2. Block copolymer particles derived from emulsion droplets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1156

Abbreviations: AFM, atomic force microscopy; CTAB, cetyl trimethylammonium bromide; DCM, dichloromethane; D/L0 , confinement dimension (Particle Diameter/Periodicity); DN, decahydronaphthalene; FITC-Dextran, fluorescein isothiocyanate-dextran; MPEG-b-PLA, methoxypolyethylene glycol-blockpoly(D,L-lactic acid); O/W, oil-in-water emulsion; PAA, poly(acrylic acid); PB, poly(butadiene); PBA-b-PAA, poly(n-butyl acrylate)-block-poly(acrylic acid); PCEA, poly-(2-cinnamoyloxyethyl acrylate); PCEMA, poly(2-cinnamoyloxyethyl methacrylate); PCEMA-b-PGMA, poly(2-cinnamoyloxyethyl methacrylate)-block-poly(glyceryl methacrylate); PEG, poly(ethylene glycol); PEO, poly(ethylene oxide); PEO-b-PCL, poly(ethylene oxide)-blockpoly(␧-caprolactone); PFOB, perfluorooctyl bromide; PGMA, poly(glyceryl methacrylate); PGMA-b-PCEMA-b-PtBA, poly(glyceryl methacrylate)block-poly(cinnamoyloxyethyl methacrylate)-block-poly(tert-butyl acrylate); PI-b-PAA, polyisoprene-block-poly(tert-butyl acrylate); PI-b-PCEMA, poly(isoprene)-block-poly(2-cinnamoyloxyethyl methacrylate); PI-b-PCEMA-b-PtBA, polyisoprene-block-poly(cinnamoyloxyethyl methacrylate)-blockpoly(tert-butyl)acrylate; PI-b-PtBA, polyisoprene-block-poly(tert-butyl acrylate); PLA, poly(lactic acid); PLA-b-PEO, poly(lactic acid)-block-poly(ethylene oxide); PLGA, poly(lactide-co-glycolide); PLGA-b-PEO, poly(lactide-co-glycolide)-block-poly(ethylene oxide); Pluronic F108, poly(ethylene oxide)block-poly(propylene oxide)-block-poly(ethylene oxide); PMMA, poly(methyl methacrylate); PPO, poly(propylene oxide); PS, polystyrene; PS-b-PB, polystyrene-block-polybutadiene; PSGMA, succinated poly(glyceryl methacrylate); PtBA, poly(tert-butyl acrylate); PtBA-b-PCEMA, poly(tert-butyl acrylateblock-poly(2-cinnamoylethyl methacrylate); PVA, poly(vinyl alcohol); r, molecular weight of a homopolymer with respect to that of its corresponding block; RES, reticulo-endothelial system; SDS, sodium dodecyl sulfate; SEM, Scanning electron microscopy; STEM, Scanning transmission electron microscopy; TEM, transmission electron microscopy; THF, tet; W/O, water-in-oil emulsion; (W/O)/W, water-in-oil-in water emulsion; XPS, X-ray photoelectron spectroscopy. ∗ Corresponding author. Tel.: +1 613 533 6996; fax: +1 613 533 6669. E-mail addresses: [email protected], [email protected] (G. Liu). 0079-6700/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.progpolymsci.2011.04.005

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2.3. 2.4.

3.

4.

5.

6.

Seeing morphologies of block copolymers confined within microspheres . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1157 Segregation behavior of block copolymer/homopolymer blends . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1158 2.4.1. Influence of copolymer/homopolymer blend composition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1158 2.4.2. Influence of homopolymer molecular weight relative to that of the copolymer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1161 2.4.3. Influence of D/L0 upon the morphologies of copolymer/homopolymer blends . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1162 Block copolymer vesicles and capsules prepared by emulsion techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1163 3.1. Capsules from block copolymer assembly and emulsification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1164 3.2. Controlled vesicle formation using microfluidic devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1165 Block copolymer self-assembly in 2D spaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1167 4.1. Assembly at the 2D interface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1167 4.2. Influence of surfactant upon surface morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1170 Emulsion as a tool to direct the formation of exotic architectures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1172 5.1. Influence of interfacial tension on the formation of budding vesicles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1172 5.2. Molecular containers and porous materials from block copolymer emulsion spheres . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1175 Perspectives and outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1178 6.1. Microphase segregation within solid emulsion particles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1178 6.2. Block copolymer vesicles through emulsification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1179 6.3. Block copolymer assembly at 2D surfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1179 6.4. Exotic and useful structures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1179 6.5. Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1179 Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1179 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1179

1. Introduction Block copolymers consist of two or more chemically distinct polymer blocks [1]. The simplest block copolymer is a diblock copolymer, An Bm , consisting of n consecutive A units and m consecutive B units. Scheme 1 shows the structures of a diblock copolymer polyisoprene-block-poly(2cinnamoyloxyethyl methacrylate) (PI-b-PCEMA) and a triblock copolymer poly(glyceryl methacrylate)-blockpoly(2-cinnamoyloxyethyl methacrylate)-block-poly(tertbutyl acrylate) (PGMA-b-PCEMA-b-PtBA) [2,3]. In the absence of strong intermolecular interactions, such as hydrogen bonding and electrostatic attraction, most polymers are incompatible above some critical molecular weights. In bulk or the solid state, the different blocks of a block copolymer segregate or

undergo self-assembly with the constituent blocks forming regularly-shaped and uniformly-sized domains that are periodically spaced. For coil–coil diblock copolymers An Bm , the shape of the segregated domains of the minority block is governed by its volume fraction, , and by block incompatibility. Fig. 1 shows the equilibrium morphologies documented for coil–coil diblock copolymers [4–6]. At a volume fraction of ∼20%, the minority block forms a body-centered cubic spherical phase in the matrix of the majority block. It changes to hexagonally packed cylinders at a volume fraction of ∼30%. Alternating lamellae are formed at approximately equal volume fractions for the two blocks. At a volume fraction of ∼38%, the minority block forms gyroid or perforated layers at moderate and high incompatibility, respectively. These interesting morphological transitions have been established experi-

Scheme 1. Block copolymers PI-b-PCEMA (top) and PGMA-b-PCEMA-b-PtBA (bottom).

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Fig. 1. Bulk segregation patterns of diblock copolymers [4]. These phases include (from left to right) spherical, cylindrical, gyroid, perforated lamellae, and alternating lamellae. Progressing from left to right, these phases are observed as the block distributions of the copolymers are increasingly symmetric. Reprinted with permission from Reference [4]. Copyright 1995 American Chemical Society.

mentally [7–11] and can be accounted for by statistical thermodynamic theories [12–20]. Furthermore, the smallest dimension of a segregated domain, e.g., the diameter of a cylinder, is proportional to the two-thirds power of the molar mass of the minority block, and can typically be tuned from ∼5 to ∼50 nm by changing the molar mass of the block [1]. In analogy to their bulk behavior, diblock copolymers also self-assemble in block-selective solvents, which solubilize one but not the other block, forming micelles with various shapes [21]. If the soluble block is long, the insoluble block aggregates to produce spherical micelles. As the length of the soluble block is decreased relative to the insoluble block, cylindrical micelles or vesicles, and micelles of other shapes can be formed, as first demonstrated by Zhang and Eisenberg [21,22]. From a single diblock copolymer, one can also effect morphological transitions of copolymer micelles by preparing micelles in different selective solvents. Normally, the transition from spherical to cylindrical and vesicular micelles is accomplished by using solvents that are increasingly poor for the core or insoluble block. ABC triblock copolymers, An Bm Cl , can also undergo self-assembly in bulk or block-selective solvents. Triblock copolymers have many more block segregation patterns in bulk than diblock copolymers, and some of the patterns are very intricate and visually striking [1]. The shapes of micelles formed by triblock copolymers in block-selective solvents are also greatly diversified. Cylindrical micelles of ABC triblock copolymers alone have included variations ranging from straight cylinders to segmented cylinders, twisted cylinders, single helices, double helices, and triple helices, etc. Fig. 2 shows a transmission electron microscopic (TEM) image and a TEM tomography image of helices formed from the self-assembly of an ABC triblock copolymer in a good solvent for A, a poor solvent for B, and a marginal solvent for C. Such a structure resembles the double helix structure seen in DNA, and is highly sophisticated [23]. Due to the synthetic challenges involved, there have not been many studies on the self-assembly of ABCD tetrablock copolymers [24–28]. The number of self-assembled patterns in either bulk or selective solvents should increase further for tetra- and penta-block copolymers. Block copolymer self-assembly is robust, and can yield various nanostructured materials for a wide range of applications. A variety of these applications are highlighted in a recent review by Kim et al. [29]. The shape diversity of discrete nanoobjects produced in block-selective solvents,

for example, should facilitate their applications in areas such as nanofabrication [3,30–37], lithography [38–40], cell cultures [41], and drug delivery [42–44]. Despite the robustness of the self-assembly strategy, there are certain limitations. For example, the cylindrical domains formed from the minority block of a diblock copolymer in bulk are packed with hexagonal ordering within grains of the size of micrometers. From grain to grain the orientation is changed. In the case of block copolymer self-assembly in block-selective solvents, the smallest dimension, e.g., the cross-sectional diameter of a strand in the double helix shown in Fig. 2b, of a self-assembled structure is typically between several and tens of nanometers. While possible [22,45,46], it is not straightforward to produce composite structures, e.g., spheres with composite internal structures, from solution self-assembly of block copolymers. A wide variety of block copolymer architectures can also be prepared through directed assembly [47]. In this review, directed assembly refers to block copolymer self-assembly under external constraints, control, or influence. These constraints can be a specific set of restricting conditions, e.g., confined volumes or 2D or 1D spaces, that are used for the self-assembly process to take place. External influence can be exerted by using external fields [48,49], including electric or magnetic fields. These influences can even include a solvent evaporation front [50], or a tailored substrate [51]. External control can also be exerted by adding foreign reagents into a system. For example, Pochan and Wooley added multiamines into their solvents to introduce interactions with the coronal poly(acrylic acid) chains of the micelles [52,53]. Using this strategy, they have been able to produce interesting and exotic structures. While a number of reviews have described various topics of emulsification [54–59], block copolymer selfassembly [1,6,21,60–65], and directed assembly [47,66], this review will focus on the intersection between these topics. More specifically, we will describe how emulsification can be used to direct block copolymer assembly, particularly through the emulsification/evaporation approach. Emulsification provides a powerful platform from which one can direct block copolymer assembly. This is especially true if the organic phase is subsequently evaporated, thus forcing the block copolymer to collapse either within an emulsion droplet, or along its surface. Significant progress has been made in recent years towards refining this technique. While the emulsion droplets serve as templates to direct the assembly, in some cases researchers have combined this with other external stimuli to achieve even higher degrees of control. Through these studies, a wide

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Fig. 2. TEM (left) and TEM tomography (right) images of double helices of PBMA250 -b-PCEMA160 -b-PtBA160 [23]. Ref. [23]. Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.

variety of exciting, and potentially useful, block copolymer assemblies have been prepared. This review will attempt to highlight the developments that have been made in this area. In Section 2, we will discuss the creation of confined volumes for block copolymer assembly. Vesicle formation through block copolymer assembly along the interfaces of emulsion droplets will be described in Section 3. Block copolymer assembly at the oil/water interface on spherical 2D surfaces, and how this may provide surface control will be discussed in Section 4. The preparation of exotic and potentially useful structures through emulsification will be described in Section 5. We will summarize our conclusions and present our perspectives on this topic in Section 6.

of copolymer concentration. This could eventually lead to solidification of the copolymer and segregation of the different blocks within the confined volumes. If the diameter (D) of the confining sphere in which a block copolymer resides is small (e.g., if D is comparable to, or smaller than, the periodicity (L0 ) of regular domains in a block copolymer), the final block-segregated structure formed by the copolymer will differ from that found in bulk or the solid state, where D can be viewed as infinitely large in the case of a bulk solid. Consequently, the selfassembly of block copolymers in confined volumes can lead to novel and interesting structures. Even if D is considerably larger than L0 , one can still obtain novel and complex block copolymer structures by the combined use of emulsification and block copolymer self-assembly [84].

2. Block copolymer self-assembly in confined volumes

2.1. Computer simulation results

Block copolymer confinement can be achieved through various routes and to varying degrees. The most attention has focussed on 1D block copolymer confinement in thin films, which has been highlighted in numerous reviews [67–69]. A recent review has also described progress in their 2D confinement within cylinders [70]. Stewart-Sloan and Thomas recently reviewed experimental and theoretical aspects of 1D, 2D, and 3D block copolymer confinement [71]. The 3D confinement of block copolymers has been achieved using aerosol droplets, initially by Thomas et al. [72], and more recently by Zhang et al. [73,74]. 3D block copolymer confinement has also been accomplished using 3D templates by Manners and coworkers [75,76], while Yabu and coworkers have confined block copolymers using a novel solvent evaporation method [77–82]. The above methods have yielded diverse morphologies that often could not be achieved in bulk. Another route towards 3D confinement is through emulsification. Emulsification is the process of breaking up a continuous organic (or aqueous) phase and dispersing, with the aid of a surfactant, the resultant oil (or water) droplets in an aqueous (or oil) medium [83]. If the dispersed droplets contain a block copolymer, solvent evaporation from the droplets causes them to shrink, and causes an increase

Computer simulation methods have been used to study the effect of spherical and cylindrical confinements on the assembly of block copolymers. Pan and coworkers observed concentric structures when they used a Monte Carlo simulation to study the self-assembly of symmetric diblock copolymers under spherical and cylindrical confinement [85], with these morphologies arising when boundary interactions were favored by one block more than by the other. It was also predicted that different phase segregated structures could be designed by simply adjusting the boundary shapes and boundary-block copolymer interactions. Fraaije and Sevink used a self-consistent-field model to study the directed assembly of diblock copolymers in nanodroplets [86]. By varying the copolymer block ratios under a fixed drop radius, a series of unique structures were found. Microphase separation and morphologies of asymmetric and symmetric diblock copolymers confined inside nanospheres with various sizes and interfacial energies have been studied by Feng et al. [87] using dissipative particle dynamics. They noted that the morphologies of the copolymers within the nanospheres are strongly influenced by both the sizes and the surface properties of the nanospheres. Recent studies using annealing Monte Carlo

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Fig. 3. Cross-sectional view of self-assembled morphologies predicted by Monte Carlo simulation for symmetrical diblock copolymers under spherical confinement at various D/L0 and ˛ values [88]. At ˛ = 1, the surface preference for the A block (shown in red) is the strongest, while at ˛ = 0, no preferential interaction between the surface and a particular block is observed. The structures below and above the dotted line correspond to ˛ values on the scales at the bottom and top of the diagram, respectively. This helps to demonstrate the dramatic range of block copolymer morphologies that may be acquired through relatively small changes of the degree of confinement and preferential interactions. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.) Reprinted with permission from Reference [88]. Copyright 2007 American Chemical Society.

simulations on the self-assembly of symmetric diblock copolymers in spherical nanopores [88], and real-space self-consistent field calculations on the self-assembly of cylinder-forming diblock copolymers under spherical confinements [89] have also revealed a rich variety of novel structures that are not possible in the bulk state. The results also show that self-assembly is largely governed by interactions between the confinement surface and the polymer chains, and the dimension of the confinement space (Fig. 3). Recently Li et al. [90] used real-space self-consistent field theory calculations to model spherically confined block copolymers with fixed degrees of confinement but varying block volume ratios and Flory-Huggins interaction parameters. Alternatively, they also kept the latter two parameters fixed to model spherically confined cylinder-forming block copolymers under various degrees of confinement, with novel structures being predicted in both scenarios [90]. Many of the above-mentioned simulation studies have shown that major parameters controlling the assembly of block copolymers in confined geometries are whether one block interacts preferentially with the boundary surface (˛) other another block, and the copolymer confinement dimension (D/L0 ). This can be highlighted by Fig. 3, which shows the diversity of structures predicted by Yu et al. [88] when these variables are altered among a series of symmet-

ric diblock copolymers. In the bulk phase, the copolymer would form a lamellar structure, while a vast array of morphologies may be obtained under the influences of confinement as well as preferential surface interactions. 2.2. Block copolymer particles derived from emulsion droplets The use of the emulsification/solvent evaporation technique to prepare copolymer microspheres began a few decades ago, with the use of poly(lactic acid) (PLA)-based copolymers to prepare biodegradable microcapsules for the controlled release of drugs. Ogawa et al. [91] dissolved leuprolide acetate in a mixture of water and gelatine to obtain the aqueous phase. The oil phase, which consisted of a solution of poly(lactic acid)-co-poly(glycolic acid) (PLGA) in dichloromethane (DCM), was slowly added to the aqueous phase under vigorous stirring to generate water-in-oil (W/O) emulsion droplets. This W/O emulsion was subsequently poured into a stirred aqueous solution containing poly(vinyl alcohol) as surfactant to produce water-in-oil-in-water ((W/O)/W) emulsions. The DCM was later evaporated from the emulsion, leading to collapse of the copolymer and capsule formation. A general summary of this procedure is shown in Scheme 2. This double

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Scheme 2. Schematic diagram showing the preparation of a water-in-oil emulsion, a water-in-oil-in-water emulsion, and subsequent formation of vesicles after evaporation of the organic solvent.

emulsion solvent evaporation technique, which was first employed by Vrancken et al. [92] to prepare homopolymer microspheres and later by Ouchi et al. [93] to prepare PLA-based copolymer microcapsules, was primarily used for the preparation of biodegradable microcapsules and microspheres for drug encapsulation and release studies. No microphase separation within the microcapsules or interfacially-driven self-assembly of the block copolymers at the 2D oil–water interface was ever reported. 2.3. Seeing morphologies of block copolymers confined within microspheres Liu and coworkers [94] were the first to report block segregation in copolymer microspheres generated from emulsification. In their system they used two diblock copolymers, including poly(tert-butyl acrylate)390 block-poly(2-cinnamoyloxyethyl methacrylate)420 (PtBA390 -b-PCEMA420 ) and poly(2-cinnamoyloxyethyl methacrylate)32 -block-poly(glyceryl methacrylate)176 (PCEMA32 -b-PGMA176 ). The former copolymer was used to form the microsphere core, while the latter was used as a surfactant to stabilize the emulsion-droplets, and later the microspheres after oil-phase solvent evaporation. The PCEMA-b-PGMA surfactant was dissolved into a minimal amount of methanol, and water was then added to form an aqueous phase (Scheme 3). PtBA390 -b-PCEMA420 was

Scheme 3. Preparation of block copolymer microspheres (copolymer = PtBA-b-PCEMA or PI-b-PtBA) by O/W emulsification (A → B) and evaporation of the organic phase (B → C). Following this, crosslinking was performed to permanently lock the structure. This could be accomplished either by photolysis of the PCEMA block (PtBA-b-PCEMA) or exposing the PI block to S2 Cl2 (PI-b-PtBA) (C → D). The PtBA domains could also be converted into PAA by hydrolysis (D → E) [94]. Adapted with permission from Reference [94]. Copyright 2001 American Chemical Society.

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Fig. 4. TEM images of thin film cross-sections of PtBA390 -b-PCEMA420 microspheres that were prepared using dichloromethane (a) or toluene (b) as the organic phase. In image (a) the circles or ellipses (c) correspond to PtBA cylindrical domains that were cut perpendicularly to the axis of the cylinders. The light stripes (d) represent PtBA cylinders that are lying flat in the plane of the image [94]. Reprinted with permission from Reference [94]. Copyright 2001 American Chemical Society.

dissolved into DCM and mixed with the aqueous surfactant solution. This mixture was stirred and sonicated, subsequently yielding an O/W emulsion. Subsequent evaporation of the DCM by mild heating at 50 ◦ C led to the solidification of PtBA390 -b-PCEMA420 . These solid spheres were then photo-crosslinked to lock in their structure, and subsequently centrifuged from the solution. TEM analysis of thin sections of the microspheres revealed that a PCEMA matrix interwoven with hexagonally-packed PtBA cylinders filled the cores of these spheres (Fig. 4a). In bulk phase the PtBA domains of PtBA390 -b-PCEMA420 formed cylindrical structures with a similar average diameter to those prepared by emulsification [94,95]. However, the degree of ordering among the structures confined in emulsion droplets differed from those prepared in bulk. The orientations of the PtBA cylinders varied inside the confined spheres (∼2 ␮m in diameter), with the cylinders facing different directions in one region of the sphere than another. Meanwhile, the analogous PtBA cylinders in the bulk films were straighter than those prepared by emulsification, and aligned in the same direction over longer distances [95]. The cylinders in the spheres bent to adapt to the confined volume encountered within the emulsiondroplets. The internal block segregation pattern changed when the emulsion droplets were prepared using DCM instead of toluene [94]. Because of the higher boiling point of toluene, a higher temperature (90 ◦ C) was used for the evaporation stage. Under this set of conditions, the resultant particles had an interior consisting of onion-like alternating layers of PtBA and PCEMA (Fig. 4b). 2.4. Segregation behavior of block copolymer/homopolymer blends If a block copolymer is mixed with one of its corresponding homopolymers, swelling of the existing morphologies may result, leading to a morphological transition [96,97]. This can also occur within block copolymer/homopolymer microspheres prepared from the emulsification protocol. Factors such as the weight (or volume) ratios

between the amount of copolymer and homopolymer (or between the homopolymer and its corresponding copolymer block) present within a blend, as well as the relative molecular weight ratios between the homopolymer and its corresponding copolymer block can affect the morphology. Therefore, adjusting the composition of copolymer/homopolymer blends within an emulsion sphere provides a means to direct the assembly in a highly controlled manner. 2.4.1. Influence of copolymer/homopolymer blend composition One of the earliest groups to study the influence of copolymer/homopolymer blends on the internal morphologies of microspheres formed via emulsion droplets was that of Liu and coworkers [98]. The morphologies of the PtBA domains within emulsion spheres could be altered by adding PtBA homopolymer (hPtBA) to polyisopreneblock-poly(tert-butyl acrylate) (PI-b-PtBA). These emulsion spheres were prepared using an O/W emulsion very similar to that described earlier for the PtBA-b-PCEMA microspheres and shown in Scheme 3. In this case, the oil phase consisted of a PI980 -b-PtBA200 /hPtBA110 blend dissolved in DCM. Meanwhile, the aqueous phase contained polyisoprene-block-poly(acrylic acid) (PI-b-PAA), which stabilized the oil droplets. Subsequent DCM evaporation caused the block copolymer to collapse, thus yielding the microspheres, which were collected and dried. The PI domains of these spheres were then crosslinked with S2 Cl2 , to lock in their structure. The PtBA block could be converted into PAA by hydrolysis, yielding porous microspheres. The internal morphologies changed with hPtBA addition, which essentially increased the total PtBA volume fraction. Without hPtBA, the internal morphologies of the PI-b-PtBA microspheres consisted of mixtures of PtBA spheres and cylinders surrounded by PI (Fig. 5a). With small amounts of hPtBA, the PtBA domains (with a volume fraction of 39%) formed worm-like structures (Fig. 5b), which Liu and coworkers attributed to a gyroid-like morphology [98]. Thus, the morphologies apparently paralleled bulk behavior, [1,4,99–101], with decreasing curvature between

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Fig. 5. TEM images of microsphere cross sections composed of PI-b-PtBA/hPtBA blends. The microspheres shown in (a) were prepared in the absence of hPtBA and had an overall PtBA volume fraction of 25%. The microspheres shown in (b) were prepared from a blend of PI-b-PtBA and had an overall PtBA volume content of 39%. The microspheres shown in (c) had an overall PtBA volume content of 54%. These samples were stained with OsO4 , which selectively stained the PI domains. The PI blocks of these samples were crosslinked with S2 Cl2 [98]. Reprinted with permission from Reference [98]. Copyright 2003 John Wiley and Sons.

the two blocks as the block distribution became more balanced, or symmetrical. However, when more hPtBA was present, yielding an overall PtBA volume fraction of 54%, the PtBA domains had an ill-defined morphology (Fig. 5c). This did not correspond with the lamellar morphology that would be anticipated for a copolymer in bulk with a symmetric block distribution. Considering that the D/L0 values among these large microspheres were above 20, it is less likely that the assembly of these structures was directed by confinement. The high weight fraction of the homopolymer (40% relative to the blend) in this latter sample may have played a role instead. Previous researchers observed macrophase segregation among copolymer/homopolymer blends when large amounts of homopolymer were present [100]. Onion-like morphologies have been observed when copolymer/homopolymer blends were confined within emulsion droplets. Significant insight into these systems has been provided by Okubo and coworkers [102,103]. They [102] studied a blend consisting of the block copolymer polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) and its homopolymers, with combinations such as PS-b-PMMA/hPS, PS-b-PMMA/hPMMA, and PS-bPMMA/hPS/hPMMA. In all cases the molecular weight of the homopolymer was lower than its corresponding copolymer block, as previous researchers had shown that the homopolymer should be no longer than its corresponding copolymer block to give a miscible blend [104,105]. Typically, a solution of PS-b-PMMA along with homopolymer(s), were dissolved into toluene. This organic phase was then mixed with an aqueous phase containing SDS as a surfactant, generating an O/W emulsion. The emulsion was then placed in an open vessel to evaporate the toluene under continuous stirring [102,103]. In their study, Okubo et al. [102] varied the weight ratio between the copolymer and the homopolymer. In this comparison, they used a lamella-forming symmetric block copolymer. Without homopolymer, the resultant particles had onion-like interior morphologies. When a blend of the copolymer and homopolymer had a PS-bPMMA/hPS weight ratio of 80/20, the particles obtained had various internal structures, including cylinder-like and bicontinuous gyroid morphologies (Fig. 6a). Meanwhile, if

the ratio of hPS was increased further, to a weight ratio of 50/50, a “sea-island” interior structure was obtained, with the “sea” composed of PS and the “islands” consisting of PMMA domains (Fig. 6b). When the homopolymer was changed to hPMMA (Fig. 6c and d), a similar general transition from lamellar to “sea island” structures occurred [102]. Okubo and coworkers [103] also quantified the relationships between the thickness of onion-like layers within emulsion spheres and copolymer/homopolymer blend composition, and also between lamellar thickness and copolymer molecular weight. Consistent with their earlier results [102], the layer thickness within these lamellar structures increased as the volume fractions of PS-b-PMMA were decreased with respect to its homopolymers, hPS and hPMMA (Fig. 7). In particular, they observed that if the homopolymers had lower molecular weights than their corresponding copolymer blocks, the layer thickness was proportional to the –1/3 power of the volume fraction of the homopolymer within the blend [103]. This trend was consistent with earlier predictions by Hashimoto et al. [100]. Within the copolymer, the volume ratios of the PS and PMMA blocks were equal, and also the blends were prepared with equal amounts of each homopolymer. Therefore, changes arose from variation of the copolymer/homopolymer volume ratios, rather than changes of relative PS or PMMA content within the blend. Onionlike morphologies were maintained throughout this series, although the concentric layers became broken when the copolymer volume was reduced to 0.1 [103]. In their earlier report, they attributed this to insufficient copolymer to form complete concentric layers at low copolymer volume fractions [102]. Changing the amount of homopolymer within a copolymer/homopolymer blend has a significant influence upon the resultant assembly structure. If a given homopolymer hA is added to an AB diblock copolymer, and the blend does not undergo macrophase segregation, hA addition can cause the blend to behave analogously to an AB copolymer with a larger proportion of the A block [106]. In effect, the added homopolymer “mimics” its corresponding block, and directs the blend’s morphological assembly. With only one block copolymer and a corresponding homopolymer (or

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Fig. 6. TEM thin cross-sectional images of particles composed of 80/20 (w/w) PS-b-PMMA/hPS (a), 50/50 (w/w) PS-b-PMMA/hPS (b), 80/20 (w/w) PS-bPMMA/hPMMA (c), and 50/50 (w/w) PS-b-PMMA/hPMMA (d). These particles were stained with RuO4 vapor [102]. Reprinted from Ref. [102], Copyright (2005), with permission from Elsevier.

alternatively a homopolymer corresponding to each block), one may potentially obtain a similar range of morphologies to that observed among a series of copolymers with a wide range of block ratios, simply by adjusting the blend composition. Considering the synthetic demands required

to generate such a wide library of block copolymers with various block ratios, copolymer/homopolymer blends provide an attractive alternative. Similarly, blends can provide a facile means to direct the assembly of a block copolymer through emulsification.

Fig. 7. TEM images of thinly sliced cross-sections of onion-like particles obtained from O/W emulsion droplets containing hPS/PS-b-PMMA/hPMMA blends. The volume fractions among the hPS/PS-b-PMMA/hPMMA blends were: (a) 0/1/0, (b) 0.1/0.8/0.1, (c) 0.2/0.6/0.2, (d) 0.3/0.4/0.3, (e) 0.4/0.2/0.4, and (f) 0.45/0.1/0.45. The samples were stained with RuO4 and the darker regions are PS domains, while the lighter regions are PMMA layers. As the volume fractions of the homopolymers increased the layers became thicker, and eventually broken layers were observed [103]. The darker regions correspond to PS regions and the lighter regions are PMMA domains. Reprinted with permission from Reference [103]. Copyright 2009 American Chemical Society.

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Fig. 8. TEM images of blend particles of PS-b-PB and hPS, with a hPS weight fraction of 50%. The molecular weight of hPS is 9.6 × 104 g mol–1 , which is approximately double the molecular weight of the corresponding PS block (r ∼ 2). The particle shown in (a) has a diameter of 340 nm and consists of one spherical lamella and one hemispherical lamella. The particle in image (b) has a diameter of 400 nm and consists of two spherical lamellae and one hemispherical lamella. The particle shown in image (c) has a diameter of 420 nm and consists of three spherical lamellae. The spherical lamellae in these images are off-center and unevenly spaced. The samples were stained with OsO4 , which selectively stains PB [107]. Reprinted with permission from Reference [107]. Copyright 2007 American Chemical Society.

2.4.2. Influence of homopolymer molecular weight relative to that of the copolymer The molecular weight ratio between a homopolymer and its corresponding copolymer block can also influence the morphology of the blend. An extensive study exploring various factors influencing the morphologies of emulsion particles composed of PS-b-PB (polystyreneblock-polybutadiene) and hPS was conducted by Jeon et al. [107]. The two copolymer blocks were approximately symmetrical, with a PS block weight fraction of 55%. They varied the degree of confinement, the weight fraction of the homopolymer, and the molecular weight of hPS relative to that of the PS block. To prepare the emulsion, PS-b-PB and hPS were dissolved in toluene and mixed with an aqueous solution containing the triblock copolymer poly(ethylene oxide)-block-poly(propylene oxide)-blockpoly(ethylene oxide) (PEO-b-PPO-b-PEO, or Pluronic F108) as a stabilizer. Once the O/W emulsion was formed, the toluene was evaporated. While the molecular weight of the copolymer remained constant throughout the study, the molecular weight of hPS was varied [107]. Three molecular weight regimes were studied, including when the molecular weight of hPS was less than (r < 1), similar to (r ∼ 1), or greater than (r > 1) that of the corresponding copolymer’s PS block. Within each regime, the effects of changes of the weight fraction of hPS and the degree of confinement were compared [107]. When the molecular weight of hPS was less than that of the PS block (r < 1), and the weight fraction of hPS relative to the PS block was increased, Jeon et al. [107] observed that the internal morphologies changed gradually from concentric lamellae (onion-like layers), to perforated lamellae to cylinders, and eventually to spheres. This behavior parallels the general trend observed among emulsion spheres by Okubo et al. [102]. The spherically confined cylinders structures were generally distorted to yield internal structures such as circular helices or stacked hoops, to accommodate their confinement within the spheres. Blends of homopolymers and copolymers are generally miscible when the

homopolymer has a lower molecular weight than its corresponding copolymer block [99,108]. In this regime, adding homopolymer can have a similar morphological effect as increasing the volume ratio of the corresponding copolymer block. Jeon et al. [107] also studied PS-b-PB/hPS blends where the molecular weight of hPS was approximately equal to that of the PS block (r ∼ 1). In these circumstances, the homopolymer should be soluble in the corresponding domains, but unable to reach the interfaces of the domain. Consequently, hPS should occupy the central region of the PS domain where it is isolated from the interfaces [108]. In addition, the PS domain should swell upon the addition of hPS [99]. A general trend among these particles was that their internal morphologies changed from onion-like lamellae to perforated lamellae, and cylindrical morphologies with increasing homopolymer weight fractions. However, many of the structures had unexpected morphologies, and the behavior varied considerably with differing particle diameters. The morphological transitions seemed to be delayed somewhat in the smaller and more confined spheres, apparently due to surface effects. In some cases, combinations of onion-like lamellae and perforated lamellae were observed in the same particle, with lamellae near the surface and perforated lamellae near the core. The conversion from lamellar to perforated lamellar morphologies apparently began near the cores of the particles, which were more isolated from the surface. Various exotic structures were obtained at higher homopolymer weight fractions, such as hoop-shaped, tetragon-shaped, figure-eight, and pretzel-shaped internal morphologies. These latter structures were apparently combinations of hoops that became fused together. The wide range of morphologies was attributed to the combination of microphase and macrophase segregations occurring under this regime, which is further enhanced by the varying degrees of confinement [107]. PS-b-PB/hPS blends with hPS molecular weights exceeding that of the corresponding PS block (r > 1) were also

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investigated by Jeon et al. [107]. Jeon et al. used hPS samples with molecular weights approximately double (r ∼ 2) or quadruple (r ∼ 4) that of the corresponding PS block. Under these conditions, the hPS and its corresponding PS block can readily phase separate from one another. When r ∼ 2, lamellar morphologies were maintained, regardless of the hPS weight fraction. However, as the weight fraction increased beyond 32%, random segregation of hPS occurred which caused these lamellar structures to become deformed. The rings of the onion-like structure were pushed off-center, so that the rings were no longer evenly distributed. Also, when the weight fraction of hPS was 50%, the outer layer was often extremely deformed, with one portion of the circular layer becoming flattened to give a hemispherical shape (Fig. 8). The PS layers became thicker as the hPS weight fraction was increased as well. Meanwhile, when r ∼ 4, the lamellar structure was also maintained as the weight fraction of hPS was varied. However, the increasing thickness of the PS layer was not observed once the homopolymer weight fraction reached and exceeded 40%. When the weight fraction was less than 40%, hPS segregated itself randomly. Meanwhile, once the weight fraction of hPS was above 40%, the hPS became segregated in the outer regions of the blend particles rather than the interior. Unlike the case when r ∼ 2, if r ∼ 4 the distance between the layers did not change significantly as the weight fraction of hPS was varied. Jeon et al. attributed this behavior to the macrophase segregation of hPS [107]. The molecular weight of a homopolymer significantly influences how its presence may direct the assembly of a copolymer/homopolymer blend. If the molecular weight of the homopolymer is well below that of the corresponding copolymer block, it can readily become incorporated into its matching block’s domains [106]. Meanwhile, homopolymers with relatively high molecular weights are more likely to undergo macrophase segregation. When the molecular weights of the homopolymer and its matching copolymer block are comparable, a combination of blending and macrophase segregation can occur, which can sometimes yield unexpected morphologies. 2.4.3. Influence of D/L0 upon the morphologies of copolymer/homopolymer blends Jeon et al. [107] also examined confinement effects on the morphologies of PS-b-PB/hPS blends. Under greater confinement, the formation of a single internal morphology becomes more favorable than a mixture of morphologies [107]. They attributed this to the greater interfacial curvatures observed in more confined droplets, which yield stronger capillary forces. The interface had greater influence upon the arrangement of the interior domains when D/L0 is small. When the diameter of the particles was 240 nm and the D/L0 value was approximately 4, the onion-like morphology was formed with only the inner lamella being perforated. This behavior was attributed to the weaker interfacial forces observed deep inside the sphere than by the layers that are closer to the surface. When the D/L0 value was increased to 5, the interior morphology consisted purely of concentric perforated lamellae (Fig. 9).

Besides the internal morphologies, the overall particle shape could also be altered. Two competing influences can affect the shape of the particles prepared by emulsification [107]. Capillary forces act to compress the matter within the particle, and these forces are spherically symmetric. Meanwhile, the free energy that arises from the morphologies of the interior domains can also affect the overall shape of the particle. This latter force can cause a particle to become distorted from a spherical shape if it is not consistent with the morphology of the interior domains. Depending on the shape of the internal morphology, spherical confinement may involve high entropic costs. Unlike under 1D or 2D confinement, there are no unconfined directions available along which a spherically confined polymer chain may realign itself to relieve frustration [89]. However, Jeon et al. observed that spherically confined copolymers may relieve this strain by distorting the overall shape of the confining particle [107]. This can occur when the interior morphology consists of hexagonally packed cylinders or helices, as well as stacked discs. If spherical particles are distorted into elliptical shapes, with the helices aligned with the major axis of the ellipse, the shape of the nanoparticle can better match the entropic demands of the interior morphologies. Such a shape distortion may occur provided that it is not outweighed by the capillary forces, which favor a spherical particle. At larger D/L0 values, spherical particles were more common than distorted particles due to the dominance of capillary forces over the entropy needs of the entrapped polymer chains [107]. When sufficient hPS had been added so that the PS-b-PB copolymer would normally form cylindrical structures in bulk, the range of morphologies varied significantly with D/L0 values. For example, when the hPS volume fraction was 51% and the D/L0 values were increased, the internal morphology generally changed from a single sphere (D/L0 = 2), to stacked discs and hoops (D/L0 ∼ 2.5–7.0), to helices (D/L0 ∼ 7–15), and towards loosely coiled cylinders (D/L0 ∼ 17) (Fig. 10). In general, the number of internal structures (such as hoops or discs) within a particle increased with increasing D/L0 . The general trend from discs towards helices or stacked discs as the confinement of cylinder-forming block copolymers was reduced parallels behavior observed by Russell and coworkers among cylindrically confined PS-b-PB copolymers [109]. Caution may be needed if one attempts to draw universal trends on the morphological behaviors of spherically confined block copolymers at this point. The behaviors of spherically confined copolymers are generally more complex than those under 1D or 2D confinement [89]. This is particularly true among asymmetric or non-lamellar block copolymers. As described earlier, the effects of adjusting confinement can generate a diverse array of copolymer morphologies [88]. The combined influence of altering confinement and blend composition can extend this variety even further, while also providing another tool to direct the assembly of a copolymer/homopolymer blend. In addition to confinement, contributing factors which direct the assembly can include the weight fraction of the homopolymer within the blend, as well as the molecular weight of the homopolymer relative to the corresponding block of the copolymer. The behavior of a confined polymer can

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Fig. 9. TEM images of PS-b-PB/hPS blend particles (a and c) and diagrams showing their corresponding morphologies (c and d). The molecular weight of hPS in these blends was 1.0 × 104 g mol–1 and the weight fraction of hPS was 34%. A TEM image (a) and schematic drawing (b) show the morphology of a blend particle with D/L0 ∼4. The outer lamella is solid while the inner lamella is perforated. A blend particle with D/L0 ∼5 and perforated layers is shown as a TEM image (c) and drawing (d) [107]. Reprinted with permission from Reference [107]. Copyright 2007 American Chemical Society.

vary depending if the confining surface is more compatible with one copolymer block over another, or if the surface has no preference [71]. This combination of factors can direct the assembly to generate complex structures that would be difficult or impossible to obtain by other means.

3. Block copolymer vesicles and capsules prepared by emulsion techniques The preparation of capsules derived from block copolymers has attracted significant attention in recent years.

Fig. 10. TEM images of thin cross-sections of particles that were prepared by emulsion from a PS-b-PB/hPS blend with a hPS weight fraction of 51% (the molecular weight of hPS was 104 g mol–1 ). Images (a) shows a particle with a D/L0 value of 2.5 which consists of two discs and one hoop, (b) shows a particle with a D/L0 value of 3.3 which contains three discs and two hoops, and (c) shows a particle with a D/L0 value of 7, which contains several discs and hoops [107]. Reprinted with permission from Reference [107]. Copyright 2007 American Chemical Society.

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Scheme 4. Schematic diagram of vesicles based on the triblock copolymer PGMA-b-PCEMA-b-PtBA [118]. The PGMA, PCEMA, and PtBA domains are shown in red, green, and black, respectively. The solutions are mixed to form an O/W emulsion (A → B). The copolymer aggregated at the oil/water interface, with the PtBA block being directed towards the interior of the oil droplets and the hydrophilic PGMA block being directed outward towards the aqueous phase. Evaporation of dichloromethane (B → C) led to the collapse of the PCEMA block, and formation of the capsule walls. These walls were structurally locked by photo-crosslinking the PCEMA domains (C → D). (For interpretation of the references to color in this scheme caption, the reader is referred to the web version of the article.) Adapted with permission from Reference [118]. Copyright 2007 American Chemical Society.

One factor driving this is their potential applications as drug delivery vehicles [110]. Numerous recent reviews [111–117] highlight some of the progress that has been made involving polymer-based capsules. Interesting vesicle systems have been prepared through the combined use of double emulsion techniques, triblock copolymers, and ternary solvents [118]. Vesicles having an aqueous cavity and whose walls are based on polymers are often called polymersomes, and are analogous to liposomes, which are based on phospholipids. Normally, polymersomes are more stable than liposomes, due to the thicker membranes provided by the polymer [119–121]. While polymersomes are often prepared using film rehydration [121] or electroformation [119] techniques, they have also been prepared by emulsification methods, such as double emulsions. In some cases, the double emulsions used to prepare polymersomes are formed with the use of microfluidic devices [122–124]. 3.1. Capsules from block copolymer assembly and emulsification Zheng and Liu have prepared vesicle-like capsules from the triblock copolymer poly(glyceryl methacrylate)-blockpoly(2-cinnamoyloxyethyl methacrylate)-block-poly(tertbutyl acrylate) [118]. This copolymer was dissolved in a small amount of a methanol and dichloromethane mixture. It was then added into a stirred oil/water mixture of decahydronaphthalene (DN), DCM, and water (Scheme 4). Since the PGMA block was water-soluble, and the PCEMA and PtBA blocks were soluble in the organic phase, the triblock copolymer assembled quickly at the oil/water interface to stabilize the oil droplets. The DCM was evaporated by mild heating, yielding droplets containing only DN within their interiors. This led to the collapse of the PCEMA block. The PCEMA block was subsequently photocrosslinked to produce vesicles with DN trapped in their cavities. The central PCEMA blocks formed the walls of

the vesicles, while the PtBA blocks were directed inwards towards the organic phase, and the PGMA blocks were projected outward into the aqueous phase. Therefore, this assembly process was driven by the need for the amphiphilic copolymer to stabilize the emulsion-droplets, with the oil/water interface effectively acting as a template. Subsequent crosslinking of the PCEMA block served to lock in these structures. While polymersomes entrap aqueous cores, nanocapsules may encapsulate hydrophobic liquids [125]. The media occupying a polymersome cavity and surrounding a polymersome are generally similar, both being aqueous. Meanwhile, the liquid within a nanocapsule’s core may differ from the continuous phase. A hydrophilic guest can be entrapped within the aqueous core of a polymersome. It has also been demonstrated that polymersomes may simultaneously carry both hydrophobic and hydrophilic guests, which are located within the polymersome wall and aqueous core, respectively [126]. Meanwhile, a nanocapsule may encapsulate a hydrophobic guest within its oil-filled core. If a nanocapsule’s liquid core differs from the surrounding media, a guest may be driven to occupy the cavity, particularly if it is more soluble in the core-filling solvent than in the continuous phase [44,127]. In addition, while a hydrophobic guest may be dissolved as a solution within the organic solvent of the vesicle cavity, in other cases the active guest may occupy the cavity as a neat liquid. For example, polyisobutylcyanoacrylate nanocapsules had been prepared which encapsulated lipidiol, a radiological tracer, as the entrapped oil [128]. More recently, lipidiol has also been entrapped within PEO-b-PPO-b-PEO nanocapsules [129]. The anticancer-drug paclitaxel could also be dissolved in the entrapped lipidiol compartment in this latter example. Block copolymer vesicles can also be prepared from (W/O)/W double emulsions. In a typical preparation, a block copolymer is dissolved in a volatile organic phase, which is then mixed with water to yield a W/O emul-

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determining the internal morphology of the capsule walls, as well as the flexibility of the capsules. 3.2. Controlled vesicle formation using microfluidic devices

Scheme 5. Formation of a polymersome from a double emulsion. The block copolymer is dissolved in the organic layer, and becomes localized at the oil–water interfaces, with the hydrophobic block (blue) projected into the oil phase and the hydrophilic block (red) projected towards the water phases. The oil phase becomes thinner during evaporation, and eventually the hydrophobic copolymer block collapses, thus forming the polymersome wall. The hydrophilic block can extend into the aqueous phases, which are both surrounding the polymersome and inside its cavity [124]. (For interpretation of the references to color in this scheme caption, the reader is referred to the web version of the article.) Reprinted with permission from Reference [124]. Copyright 2006 American Chemical Society.

sion. Following this, the W/O emulsion is then added to an aqueous phase, to yield a (W/O)/W emulsion upon mixing. The organic phase is then evaporated from the (W/O)/W emulsion. As this occurs, the copolymer becomes more concentrated and aggregates along the oil–water interfaces, and eventually the hydrophobic block collapses (Scheme 5). This yields water-filled capsules whose walls are composed of the copolymer. The hydrophilic block will normally be projected into the aqueous phase both inside and outside the polymersome (thus acting as a corona), while the collapsed hydrophobic block forms the “core” of the polymersome wall. Recently Shim et al. [130] prepared microcapsules from blends of the copolymer poly(styrene)-blockpoly(butadiene)-block-poly(styrene) (PS-b-PB-b-PS) and hPS using this general approach (Scheme 6). The microcapsules could be separated to isolate those of a desired size through selective sedimentation. Since both the PS and PB blocks were hydrophobic, they both collapsed and were confined within the capsule wall as the organic phase was evaporated. Therefore the structures of the capsule walls differed from that typically seen among polymersomes, as there were no hydrophilic blocks extending into the aqueous phase. Furthermore, microphase segregation of the PS and PB domains occurred within these thin walls. The internal morphology could be tuned by varying the hPS content within the PS-b-PB-b-PS/hPS blends. Without hPS, the internal morphology of the polymersome walls consisted of PS cylinders surrounded by PB. Increasing hPS content within the copolymer/homopolymer blend resulted in morphological changes from PS cylinders, to lamellae, to PB cylinders, and finally to PB spheres. Among these morphologies, the lamellae and the cylinders were mainly aligned parallel with the surfaces of the capsule walls. Because the PB domains were more flexible than those of PS, addition of hPS also changed the mechanical properties of the polymersomes. The capsule walls were more rigid if they were prepared from blends with higher hPS content. The (W/O)/W emulsion droplets served as templates to direct the overall assembly of the capsules. Meanwhile, the blend composition played a key role in

In recent years, the development of microfluidic devices has aided research in various areas of chemistry and biology [131]. Microfluidic devices have also been applied towards emulsion chemistry [132], and this technology has been applied to preparing unique diblock copolymer assemblies [122–124,133]. Key advantages of microfluidic devices are the monodispersity of the resultant particles, and the ease of adjusting the droplet diameters. Because the D/L0 values have a strong influence on the morphologies of the block copolymers, control of the droplet diameters can be used to tune the morphology of the diblock copolymer. In contrast to traditional double emulsions, which involve two main steps, a microfluidic device can allow the preparation of a double emulsion in one step [123]. In common with traditional double emulsions, the confinement of the copolymer at the interfaces between the oil phase and the water phase is used to direct the assembly of the polymersomes. Because the size distribution of the (W/O)/W droplets obtained using microfluidic devices are narrow, monodisperse polymersomes can be prepared using these double emulsions as templates. Similar to their traditional double emulsion counterparts, double emulsions prepared by microfluidic devices can also yield polymersomes upon organic phase evaporation. Since the diameters of these droplets can be readily controlled, the diameters of the resultant polymersomes can be adjusted also. In 2005, Weitz and coworkers [122,123] used a microfluidic device to prepare a (W/O)/W double emulsion, which yielded polymersomes composed of the diblock copolymer poly(n-butyl acrylate)-blockpoly(acrylic acid) (PBA-b-PAA). This device consisted of two tubes with circular cross-sections that were inserted into a glass tube with a square cross-section (Fig. 11a). One of these circular tubes served as an injection tube, while the other formed a collection tube. An inner aqueous fluid flowed through the injection tube, while an intermediate organic solution flowed in the same direction in the region surrounding this tube. The copolymer was dissolved in this intermediate organic phase. Meanwhile, an outer aqueous solvent flowed through the square capillary surrounding the collection tube from the opposite direction. Once these fluids met, the outer fluid reversed its direction to flow along with the other two fluids. These three solvent phases were focused through a narrow opening into the collection tube, and formed droplets after passing through this constricted opening. The size of the droplets could be adjusted by changing the size of this opening. Weitz and coworkers noted that the diblock copolymer played a critical role in stabilizing (W/O)/W emulsiondroplets generated by these devices. Without the copolymer, the interior droplet broke through the intermediate organic phase and merged with the outer aqueous phase [122]. Therefore, the assembly of these polymersomes is directed by demand for the amphiphilic copolymer to reduce the overall interfacial tension between the oil and

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Scheme 6. Preparation of PS-b-PB-b-PS/hPS capsules from a (W/O)/W emulsification. This diagram highlights the solvent evaporation stage. PEO-b-PPOb-PEO was used as a stabilizer. The PS-b-PB-b-PS/hPS blend became localized within the capsule wall, and the internal morphology was dependent upon the hPS content in the blend [130]. Reprinted with permission from Reference [130]. Copyright 2010 American Chemical Society.

Fig. 11. A diagram of the microcapillary system used by Weitz and coworkers to prepare double emulsion droplets (a). The inner and outer fluids are aqueous phases, while the middle fluid is the organic phase [133]. A more recent device developed by Weitz and coworkers is shown in image (b), which allows loading of two inner aqueous fluids forming separate droplets, and subsequently multicompartment polymersomes. The two inner aqueous fluids may contain different hydrophilic guests, which will be isolated from one another. Conceptual (c) and overlays (d and e) of optical and fluorescence microscope images of PEG-b-PLA polymersomes with aqueous compartments loaded with FITC-Dextran (green) and PEG (white in image c, grey in images d and e) [135]. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.) Image (a) reprinted from Reference [133]. Copyright 2008 American Chemical Society. Images (b–e) reprinted from: Ref. [135]. Copyright 2011 Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.

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water phases. In addition, the interior aqueous droplet serves as a template to determine the size of the polymersome shell [123]. The number of vesicles formed within the droplets can vary, depending on whether the intermediate organic or the inner aqueous fluid forms droplets first. If the innermost aqueous phase forms droplets first, multiple water droplets will be suspended inside a larger oil droplet. On the other hand, if the interior and intermediate solutions form droplets simultaneously, the resultant droplets will contain one inner aqueous droplet surrounded by an organic middle phase and a (W/O)/W double emulsion is thus formed. The organic phase is subsequently evaporated, and the organic layer becomes thinner, and eventually forms a membrane composed of the diblock copolymer. Weitz and coworkers [122] noted that the thickness of the vesicle membrane varied depending on the concentration of the diblock copolymer. Weitz and coworkers [134] recently demonstrated that adjusting the solvent content of the organic phase provides another level of control. Their organic phase here was a solvent mixture with a volatile good solvent (chloroform) and less volatile poor solvent (hexane) for the PEG-b-PLA copolymer [134]. The more volatile chloroform is preferentially lost to the continuous phase, leading to a dewetting process yielding polymersomes. At lower chloroform volume ratios, the two copolymer monolayers at the middle-outer and innermiddle interfaces were more likely to adhere together to yield polymersomes, expelling remaining organic solvent mixture in the process. However, if the organic phase had insufficient chloroform, the copolymer would precipitate without yielding polymersomes. Therefore, by adjusting the solvent ratios in the organic phase, they could therefore control how readily a double emulsion would yield polymersomes, and also the strength of the polymersome walls [134]. Recently, Weitz and coworkers [135] prepared nonspherical, multi-compartment polymersomes of PEG-bPLA, which could encapsulate different hydrophilic guests within the different inner aqueous droplets. This was accomplished by modifying their microcapillary system so that it incorporated two parallel injection tubes (Fig. 11b) delivering the inner aqueous phase [135,136], rather than one such tube. This system allows the loading of different hydrophilic guests into separate inner aqueous droplets of the double emulsion and hence the resultant polymersomes, without cross-contamination, which they demonstrated using aqueous phases carrying PEG and FITC-Dextran (Fig. 11c–e). Weitz and coworkers [135] suggested that these polymersomes could be useful for carrying reagents that need to be isolated from one another until an appointed time, when the reagents could be mixed by breaking down the polymersomes. The inner droplets and the surrounding diblock copolymer membranes were clustered together, giving these particles their non-spherical shape. Various approaches to prepare non-spherical particles through microfluidic devices have recently been highlighted in a review by Weitz and coworkers [137]. Polymersomes were also prepared by microfluidic devices incorporating cross-junctions or T-junctions, as demonstrated by Weitz and coworkers [138], and by

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Colin and coworkers [139], respectively. The crossjunction device used by Weitz was composed of poly(dimethylsiloxane) (PDMS) which was coated with glass to improve its resistance to organic solvents, and could also allow subsequent functionalization to control the hydrophobicity of the channels, and hence their wettibility. This could help to prevent fouling of the devices by block copolymer deposition [138]. Meanwhile, the device used by Colin and coworkers was made up of fused silica, which had good compatibility with organic solvents. In both systems, the inner aqueous phase was fed through the main channel or capillary, and the middle organic and outer aqueous phases were fed perpendicularly into the main channel to create the double emulsions. The device used by Weitz and coworkers [138] used two middle phase organic cross junctions, so that the organic solvent mixture could be tuned. Meanwhile, Colin and coworkers showed that they could obtain a high degree of control over their resultant polymersomes by adjusting the relative flow rates of the inner, intermediate, and outer phases, which allowed tuning of the number of inner droplets, as well as the diameters of the inner droplets and the overall polymersomes [139]. Although the principles of emulsification prepared by microcapillary devices parallel those of traditional emulsions, a key benefit of this technology is the level of control provided. These devices effectively behave as templates to further direct the assembly of the polymersomes. Microcapillary systems can generate monodisperse droplets of a particular diameter, thus yielding monodisperse polymersomes. In addition, they allow one to readily control whether the double emulsion droplets encapsulate a single smaller droplet, or multiple droplets. A current limitation of microfluidic devices is the quantity of material that can be prepared. Weitz and coworkers have suggested that this hurdle may be overcome through the use of parallel devices [137]. 4. Block copolymer self-assembly in 2D spaces While emulsification provides an effective method to direct block copolymer assembly inside particles, it can also be used to direct the self-assembly of block copolymers on their surfaces. With this approach, one of the blocks of a given copolymer should be soluble in a solvent used for the emulsification, while the other block(s) should be insoluble in that solvent. As observed during vesicle formation from double emulsions, the amphiphilic block copolymer is driven to the interface between the oil and water phases. However, in these cases the assembly generally occurs along one interface instead of two, or on the surface of a structure. Confining self-assembly onto the surfaces of emulsion-droplets can yield structures with interesting surface morphologies, and allow control of the surface composition. Sometimes the surfactant can determine the surface composition, even if it is not incorporated into the final structure. 4.1. Assembly at the 2D interface Liu and coworkers demonstrated that emulsification could be used to prepare spheres having segregated domains on their surfaces [140]. They used a combination

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Scheme 7. The structures of the block copolymer surfactant PCEMA-b-PGMA (top left) and the PCEA homopolymer (top right). The PSGMA block (bottom) of the PCEMA-b-PSGMA surfactant is also shown. The PSGMA block was obtained by succinating 69% of the hydroxyl groups in the PGMA block. Various possible substitutions of the two hydroxyl groups of this block are shown [140].

of two water-soluble block copolymers, poly(2cinnamoyloxyethyl methacrylate)-block-poly(glyceryl (PCEMA-b-PGMA) and poly(2methacrylate) cinnamoyloxyethyl methacrylate-block-poly(succinated glyceryl methacrylate) (PCEMA-b-PSGMA), as surfactants (Scheme 7) to stabilize oil droplets in an O/W emulsion. Therefore, the hydrophobic blocks of these surfactants were identical, while their hydrophilic blocks differed. The oil phase consisted of a DCM solution of the homopolymer poly-(2-cinnamoyloxyethyl acrylate) (PCEA). When the concentrations of both surfactant copolymers were equal, Liu and coworkers [140] anticipated that both of the surfactants would quickly stabilize an oil droplet suspended in an aqueous solution, without regard for incompatibilities between their water-soluble PGMA and PSGMA blocks. Initially the surfactants were randomly distributed along the surfaces of the oil droplets, with the hydrophilic PGMA and PSGMA chains extending into the aqueous phase, and the PCEMA chains facing the organic phase. However, once the droplets were sufficiently stable, the surfactants could then reorganize themselves on the 2D surface, creating segregated PGMA and PSGMA domains (Scheme 8). The surfactant’s PCEMA blocks and the PCEA homopolymer collapsed upon removal of the organic phase. This yielded spheres with PCEA cores and surfactants positioned along their surfaces, with their PCEMA blocks facing the core and their hydrophilic blocks extending into the aqueous phase. The PCEMA blocks were subsequently photo-crosslinked, which permanently locked the structures.

Scheme 8. Schematic diagram of the formation of bumpy particles, with bumps composed of PSGMA (green) and surrounding surfaces composed of PGMA (blue) [140]. Initially the aqueous and the organic phases were mixed to form the emulsion droplets, and once the droplets were stabilized, PCEMA-b-PGMA and PCEMA-b-PSGMA segregated themselves according to their hydrophilic blocks (A → B). Dichloromethane was gradually removed, leading to the collapse of the PCEMA block and PCEA. During this collapse, electrostatic repulsions between the PSGMA blocks caused them to form bumps on the particle surface (B → C). PCEA formed the particle’s core, while the surfactant copolymers were positioned along the surface, with their PCEMA blocks extending into the sphere and their hydrophilic PGMA or PSGMA blocks directed towards the aqueous phase (C). Subsequently the structures are locked in by photo-crosslinking (C → D). (For interpretation of the references to color in this scheme caption, the reader is referred to the web version of the article.) Reprinted with permission from Reference [140]. Copyright 2005 American Chemical Society.

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Fig. 12. TEM (a) and AFM phase-contrast (b) images of PCEA microspheres with surfaces consisting of PGMA and PSGMA domains. The bumpy microspheres shown in the TEM image were prepared in the presence of CuCl2 and stained with uranyl acetate. The flat regions of the surface correspond to the PGMA domains, while the bumps on the surface are occupied by the PSGMA domains (a). The microspheres shown in image (b) were prepared in the presence of NaCl instead of CuCl2 . Although the bumpiness was reduced in the presence of NaCl, the contrast visible in the lighter regions suggests that segregation of the PGMA and PSGMA domains had occurred [140]. Reprinted with permission from Reference [140]. Copyright 2005 American Chemical Society.

TEM and atomic force microscopy (AFM) images (Fig. 12) indicated that the PGMA and PSGMA domains had segregated themselves along the 2D surfaces of the droplets, thus forming bumps on the surfaces of these spheres. The bumps consisted of PSGMA while the flat surface regions were composed of PGMA. These bumps arose from electrostatic repulsions between the carboxyl groups of the PSGMA chains as they became more crowded in the absence of DCM [140]. The bumps could be made taller or shorter by adding either CuCl2 or NaCl, respectively, into the aqueous phase during the emulsion preparation. These additives helped tune the assembly by bridging the PSGMA chains (CuCl2 ) or by screening the electrostatic repulsions between those chains (NaCl). ABC triblock copolymers can also form hierarchical assemblies on the surfaces of emulsion droplets. Liu and coworkers [141] prepared cylindrical and spherical micelle-like aggregates of the triblock copolymer polyisoprene110 -block-poly(2-cinnamoyloxyethyl methacrylate)150 -block-poly(tert-butyl)acrylate320 (PI110 b-PCEMA150 -b-PtBA320 , Scheme 9). From these micelle-like aggregates, they then prepared hierarchical superaggregates of these structures by allowing them to congregate on the emulsion droplet surfaces. The preparations of the spherical and the cylindrical micelle-like aggregates differed somewhat (Scheme 10) [141]. To prepare cylindrical micelles, the copolymer was heated in the block-selective solvent decahydronapthalene, which is selective for the PtBA and PI blocks. Spherical micelles were prepared by initially dissolving the copolymer in a good solvent such as DCM, and subsequently adding DN to this solution. After this, the DCM solvent was removed, causing the PCEMA block to collapse. These cylindrical or spherical micelle-like aggregates essentially served as building blocks for the hierarchical structures subsequently prepared on the surfaces of the emulsion droplets.

Once either the cylindrical or spherical micelles were formed, a second block-selective solvent (methanol) was added to the micellar solutions that were dispersed into DN, and the mixture was stirred [141]. Methanol is not miscible with DN, and it is selective for only the PtBA block. Therefore, the micelles aggregated on the surfaces of the methanol droplets, with their PtBA blocks stretched into the methanol droplets, and the PI blocks projected out into the surrounding DN solution. While many emulsions utilize an organic and aqueous phase, in this example both of the immiscible phases were organic solvents. The micelle-like aggregates formed flower-like superaggregates and ribbon cage-shaped structures at 22 and 52 ◦ C, respectively (Fig. 13). These structures formed at their corresponding temperatures regardless of whether they had spherical or cylindrical micelles as precursors, suggesting that these were equilibrium structures. Therefore, temperature performed a role in directing the assembly of these hierarchical structures.

Scheme 9. Structure of polyisoprene110 -block-poly(2-cinnamoyloxyethyl methacrylate)150 -block-poly(tert-butyl)acrylate320 (PI110 -bPCEMA150 -b-PtBA320 ).

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Scheme 10. Schematic diagram summarizing the preparation of spherical and cylindrical micelle-like aggregates from PI-b-PCEMA-b-PtBA, followed by emulsification between two poorly miscible solvents (DN and methanol) to yield flower-like superaggregates or ribbon cage structures by assembly at 22 or 52 ◦ C, respectively. Flower-like superaggregates or ribbon cage structures were obtained through assembly at their corresponding temperatures, regardless of whether spherical or cylindrical micelle-like aggregates were used [141]. The inset image shows cylindrical micelle-like aggregates before (A) and after (B) assembly in methanol. The micelles aggregate at the surfaces of the DN droplets. The central cylinder is composed of PCEMA (red) while the PI (blue) and PtBA (light blue) chains extend outward from the PCEMA domain. (For interpretation of the references to color in this scheme caption, the reader is referred to the web version of the article.)

4.2. Influence of surfactant upon surface morphology Surfactants play a critical role in emulsification, as they reduce the interfacial tension between the oil and water phases. This in turn helps the emulsion system overcome the penalty arising from the increased overall surface area between the two phases as the diameters of emulsiondroplets are reduced. In addition to this more traditional role, surfactants can also direct the assembly of block copolymer emulsions, particularly by determining the surface composition of these structures. This can occur even if the surfactant itself is not incorporated into the final assembly structure. As suggested above, the nature of the surfactant can determine which copolymer block will form the exposed surface of an emulsion particle. Okubo and workers [142], observed this when they varied the aqueous surfactants stabilizing oil droplets of polystyrene-blockpoly(methyl methacrylate) (PS-b-PMMA) dissolved in toluene. The surfactants included either sodium dodecyl sulfate (SDS), poly(vinyl alcohol) (PVA), poly(oxyethylene nonyl phenyl ether) (Emulgen 911), or poly(oxyethylene sorbitan monooleate) (Tween 80). Regardless of which surfactant was used, spherical particles composed of onion-like alternating PS and PMMA layers were obtained after the toluene was evaporated. However, the domain that formed the surface layer differed according to the surfactant, with the block that was more compatible with the chosen surfactant forming the surface layer. When

either SDS or PVA was used, PMMA formed the surface layers of the resultant particles. Meanwhile, if either Emulgen 911 or Tween 80 was used, the resultant particle surfaces were composed of PS. Analysis of interfacial tension indicated that the surface layers were determined by whichever block provided the least surface tension with the surfactant-bearing aqueous phase. These experimental observations that the block most compatible with the surrounding formed the particle surface were consistent with the Monte Carlo simulations by Yu et al. [88]. Jeon et al. [143] observed similar behavior among emulsion particles composed of polystyrene-blockpoly(butadiene) (PS-b-PB) and the polystyrene homopolymer (hPS). These particles were also prepared from O/W emulsions, with the oil droplets containing the copolymer/homopolymer blend dissolved into toluene, which was subsequently evaporated to yield the particles. The oil droplets in the O/W were stabilized by the amphiphilic block copolymer surfactants polystyrene-block-poly(ethylene oxide) (PS-b-PEO) and polybutadiene-block-poly(ethylene oxide) (PB-b-PEO). In agreement with the results of Okubo and workers [142], the block that was most compatible with the prevailing surfactant formed the surface layer. Therefore, when PS-b-PEO was used as the surfactant, the surfaces of the resultant particles were composed of PS (Fig. 14a–c). Meanwhile, if PB-b-PEO was used to stabilize the oil droplets, the outer layer of the particles was composed of PB (Fig. 14i–k). Because the PS-b-PB copolymer was sym-

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Fig. 13. TEM images of spherical micelle-like aggregates (a) and flowery superaggregates (b) formed at 22 ◦ C two days after the initial addition of MeOH. Also shown are cylindrical micelle-like aggregates (c) and corresponding ribbon cages formed at 52 ◦ C three days after the addition of MeOH (d). All specimens were stained with RuO4 for 2 h [141]. Reprinted with permission from Reference [141]. Copyright 2008 American Chemical Society.

metric, onion-like lamellar structures (Fig. 14a and i) were obtained in the absence of hPS. The internal morphologies changed to cylindrical PB helices (Fig. 14b and j) and PB spheres (Fig. 14c and k) as the volume fraction of hPS was increased. The morphologies became more complex when mixtures of the PS-b-PEO and PB-b-PEO surfactants were used [143]. The surface morphologies, and even the overall particle shapes, varied significantly in this case. In the absence of hPS, shapes of the particles changed from PB-covered spheres (Fig. 14i), to tulip-bulb shaped structures (Fig. 14f), to striped elliptical particles (Fig. 14g), to reversed tulipbulb shaped particles (Fig. 14d), and finally to PS-covered spheres (Fig. 14a) as the surfactant mixture was changed from solely PB-b-PEO, to mixtures of the two surfactants with increasing PS-b-PEO content, until the surfactant mixture was composed solely of PS-b-PEO. The surfactant composition directed the surface morphology and shapes of the droplets, with a mixture of PS and PB domains being exposed when a mixture of surfactants was present. The tulip-bulb shape formed because the symmetric PS-b-PB

copolymer could not maintain alternating PS and PB layers over a spherical particle due to the lack of either PS(Fig. 14f) or PB-bearing surfactant (Fig. 14d). When the surfactant mixture was composed of an approximately equal mixture of PS-b-PEO and PB-b-PEO, the particles acquired an elliptical shape (Fig. 14g). This shape was attributed to anisotropic interfacial energy [144], as well as entropy [145]. The surfaces that were covered by alternating PS and PB domains had lower curvatures to avoid loss of entropy due to bending of the polymer chains. At the ends of the ellipse, the curvature was higher, and only one polymer domain occupied these regions. The combined effect of simultaneously using mixed surfactants and varying the composition of the PS-bPB/hPS blend was also studied. In these cases oblate discs which were axially penetrated by PB cylinders (Fig. 14e) were observed when both the surfactant and copolymer/homopolymer blend consisted of intermediate mixtures. As hPS content was increased further, the minor PB domain changed from cylinders to spheres, yielding spherical PB domains surrounded by a PS matrix (Fig. 14h).

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Fig. 14. Graphical summary of the combined role of surfactant composition and homopolymer volume fraction on directing the assembly of PS-b-PB/hPS blends. The horizontal axis represents the hPS volume fraction within the blend, while the vertical axis represents the PS volume fraction among the surfactants PS-b-PEO and PB-b-PEO out of the total volume of PS and PB blocks. The lighter domains represent PS domains, while the darker domains are PB domains [143]. Ref. [143]. Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.

These PB spheres were distributed throughout the interior, and also exposed to the surfaces of the particles. These reports helped demonstrate how emulsion particle surfaces could be modified by changing the surfactant composition. The copolymer block that is most compatible with the prevailing surfactant will generally form the outer layer [142,143]. When a mixture of surfactants was used, with each surfactant being more compatible with a different copolymer block, a diverse array of structures was obtained. Both of the copolymer blocks became exposed to the surface, and the overall shapes of the resultant particles varied also. Careful choice of the surfactant can thus provide a potent means to direct block copolymer assembly. As demonstrated by Jeon et al. [143], this structural diversity could be extended further by also varying the copolymer/homopolymer blend composition, providing an additional dimension of control over the assembly.

5. Emulsion as a tool to direct the formation of exotic architectures Emulsification can yield a variety of complex micellelike block copolymer aggregates, as well as particles with exciting applications. Some examples of these complex structures have been described earlier in this review, including the flower-like and ribbon cage structures prepared by Hu et al. [141], as well as the non-spherical tulip-bulb shaped particles observed by Jeon et al. [143] when they used mixed surfactants to stabilize their emulsions. This section will highlight approaches that have led to the preparation of complex block copolymer aggregates. Some of the structures described in this section were obtained by combining emulsification techniques

with the use of copolymer/homopolymer blends, microcapillary systems, or also by obtaining kinetically trapped vesicles from the breakdown of larger emulsion droplets into smaller emulsion droplets. These approaches may offer high degrees of control, so that one can readily tune the morphologies of their target structures.

5.1. Influence of interfacial tension on the formation of budding vesicles Emulsion droplets can become unstable and break down into smaller droplets if the interfacial tension between the emulsion droplet and the continuous phase is reduced. This situation has been utilized to prepare block copolymer assemblies [146,147], and the process is similar to that of a spontaneous emulsion [148,149]. As the solvent is gradually removed from an emulsion droplet, the block copolymer’s concentration increases inside the droplet. This causes the amphiphilic block copolymer to aggregate at the oil/water interface, thus behaving as a surfactant, and causing the interfacial tension between the droplet and continuous phase to decrease [150]. As a result, the droplets may eventually break down to form smaller droplets (which have a larger total surface area per given volume), and sometimes release the copolymer into the solution as micelle-like aggregates. Geng and Discher [151,152] used this approach to prepare worm-shaped micelles from poly(ethylene oxide)-block-poly(␧-caprolactone) (PEO-bPCL). Hayward and coworkers [146,147,153] have also utilized this method to prepare micelles from PS-bPEO/hPS blends. Zhu and Hayward prepared emulsions by initially dissolving PS-b-PEO into chloroform [146]. In some

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experiments they dissolved the copolymer by itself, while in other cases the copolymer was mixed with hPS as a blend. An O/W emulsion was prepared by mixing this oil phase by hand with an aqueous solution containing PVA surfactant. The droplet diameters in this hand-shaken emulsion were large, ranging between 5 and 100 ␮m. As the organic phase was gradually evaporated and the polymer concentration increased, the droplet surfaces roughened, and subsequently the droplets broke down into smaller droplets (with diameters below 1 ␮m) and threads. Among the PS-b-PEO systems, as the chloroform was removed, the equilibrium apparently favored formation of PS-b-PEO aggregates that were dispersed into water [146]. The PS block formed the core while the water-soluble PEO block formed the corona. When Zhu and Hayward varied the weight fraction of the PEO block among their diblock copolymers, the morphologies of the micelles ranged from predominantly spherical micelles when the PEO weight fraction was 65%, to predominantly worm-like micelles when the PEO weight fraction was 34%. This trend agrees with observations by Geng and Discher [152], who noted that with increasing hydrophilic PEO volume fractions among their PEO-b-PCL copolymers, spherical micelles became favored over worm-like micelles. This behavior also paralleled that reported Jain and Bates [154], when they varied the weight fraction of PEO among a series of PB-b-PEO copolymers. Meanwhile, the diameters and morphologies of the worm-like micelles could be controlled by adjusting the homopolymer content within the PS-b-PEO/hPS blends [146]. When the weight percentage of hPS was 70%, pearl necklace structures were observed, which apparently formed intermediate structures between cylinders and spheres. Once the weight percentage of hPS was increased further to 80%, spherical micelles could be seen along with the pearl necklace structures (Fig. 15). In a related study, Zhu and Hayward [147] used a microfluidic device (Fig. 16) to prepare O/W emulsion droplets containing PS-b-PEO. As the chloroform solvent was subsequently evaporated from the copolymer-bearing oil droplets, “budding vesicles” formed on the droplet surfaces (Fig. 17a). Zhu and Hayward suggested that the formation of these budding vesicles parallels the budding mechanisms of lipid and block copolymer vesicles [147,155]. These results were compared to those in a PSb-PEO/hPS blend. When hPS was present at a 50% weight fraction, dendritic particles formed, which had narrow cylindrical arms reaching out from their surfaces (Fig. 17b). These arms apparently formed during the initial stages of interfacial instability, and become trapped due to the presence of the homopolymer. As proposed by Zhu and Hayward, the hPS effectively behaved as a selective solvent for the PS block, and thus affected its interfacial interactions and curvature. The homopolymer also slowed the kinetics of the system by replacing solvent molecules with polymer chains, thus slowing the breakdown of the original droplet into smaller droplets [146]. The weight fraction of the PEO block among PEOb-PS copolymers also influenced the breakdown of the emulsion droplets into smaller droplets [147]. While budding vesicles formed among emulsion droplets containing

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copolymers with larger PEO weight fractions (such as 35%), they were not seen when the copolymer had lower PEO weight fractions (15%) when spherical particles with rough surfaces formed instead. These rough surfaces provided increased surface areas, indicating that the interfacial tension had decreased, but not to the point where budding vesicles were generated. Budding vesicle formation was therefore is inhibited at lower PEO weight fractions. The reduced hydrophilic PEO weight fraction may have counteracted any decreases of interfacial tension that would have been observed otherwise. The influence of a block copolymer’s composition upon the interfacial tension of the droplets and the subsequent influence on the resultant morphologies was recently described as part of a review by Hayward and Pochan [150]. Hayward and coworkers [153] observed that varying the surfactant concentration also affected the interfacial tension of droplets containing PS-b-PEO in a similar manner as changing the weight fraction of the PEO block (Fig. 18). With increasing SDS concentration, the resultant morphologies of PS-b-PEO (with molecular weights of 3.7 × 104 and 6.5 × 103 g mol–1 for the PS and PEO blocks, respectively) particles yielded either spherical particles with rough surfaces (0.1 mg/mL SDS), budding vesicles (0.2–0.7 mg/mL SDS), and eventually released the copolymer as worm-like vesicles (1 mg/mL SDS). At higher SDS concentrations (∼5 mg/mL), spherical micelles were favored over worm-like micelles [153]. A similar trend was observed when PVA was used as the surfactant, but much higher concentrations were required to obtain a similar effect as produced by SDS. As mentioned earlier, the groups of Okubo and workers [142] and Jeon et al. [143] have demonstrated that surfactant composition can direct the morphology of emulsion droplets. It is apparent from Hayward and coworkers’ [153] results that surfactant concentration may direct this assembly also. Therefore, not only choice of surfactant, but also its quantity, may direct emulsion particle assembly. Surface protrusions were also observed by Tsapis and coworkers [156], among O/W emulsions incorporating blends of poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG) and poly(lactide-co-glycolide) (hPLGA). The copolymer/homopolymer blends were dissolved in the oil phase, which was a mixture of DCM and perfluorooctyl bromide (PFOB), and the oil phase was subsequently evaporated. During the evaporation, DCM was removed, while the less volatile PFOB remained and phase segregated from the rest of the oil phase as a PFOB droplet. Unlike DCM, the PFOB was a poor solvent for the copolymer, and hence the copolymer blend became concentrated in the remaining DCM surrounding the PFOB droplet, thus forming the capsule wall. Therefore, the PFOB droplets eventually formed the capsule cores. Despite its solubility in water, it was noted that PEG actually favors DCM [157,158]. However, at a critical point during the evaporation, insufficient DCM remained to solubilize the PEG chains, which then extended into the aqueous phase. The interfacial area increases with increasing PLGA-b-PEG concentration to provide greater contact between the aqueous phase and the PEG blocks. Thus, the need to increase the surface area of the droplets in order to expose

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Fig. 15. Bright field TEM images of PS-b-PEO/hPS blends with hPS weight fractions of 60% (a), 70% (b), and 80% (c). At a hPS weight fraction of 60%, a mixture of cylinders and pearl necklace structures are present. The pearl necklace structures apparently correspond to an intermediate morphology between cylindrical and spherical structures. The pearl necklace structures became dominant at a weight fraction of 70% hPS. When the weight fraction of hPS was increased further to 80%, both pearl necklace and spherical structures were present [146]. Reprinted with permission from Reference [146]. Copyright 2008 American Chemical Society.

the PEG domains to the aqueous phase apparently drove the assembly of these protruding structures. The surface morphologies of the capsules varied depending upon the PLGA-b-PEG/hPLGA blend content, with more extensive hair-like protrusions growing from capsules with higher copolymer content (Fig. 19). This behavior was consistent with observations by Gref et al. [159], who reported that microparticles composed of hPLA and PLA-b-PEG had smooth and rough surfaces when they were made up of hPLA and PLA-b-PEG, respectively.

Understanding the transitions that occur with changing interfacial tension at the surfaces of emulsion droplets can provide a helpful tool for particle design, and may allow one to tune the surface areas and morphologies of the particles generated. As described above, one can kinetically trap the breakdown of emulsion droplets at various stages. This can be accomplished by controlling factors such as the block distribution within an amphiphilic copolymer, the concentration and choice of surfactant, the nature of the copolymer/homopolymer blend, or the length of the evap-

Fig. 16. Microfluidic device used by Zhu and Hayward to prepare uniform chloroform droplets containing PS-b-PEO suspended in the aqueous phase [147]. The aqueous phase was a 1/1 (v/v) mixture of water and glycerol, and PVA was dissolved in this phase to stabilize the droplets. Ref. [147]. Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.

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Fig. 17. SEM images of (a) PS-b-PEO budding vesicles which formed during chloroform evaporation from emulsion droplets and (b) dendritic particles of a blend of PS-b-PEO and hPS which formed during the evaporation of chloroform from the emulsion droplets. The inset images of (a) and (b) are TEM images obtained after the samples were stained with RuO4 [147]. Ref. [147]. Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.

oration time. Careful control of these conditions may yield particles with a desired surface area or surface roughness through directed assembly.

5.2. Molecular containers and porous materials from block copolymer emulsion spheres The preparation of supramolecular hosts and porous materials is of great interest, particularly if they can be used as hosts for smaller molecules within the void spaces on their surfaces or in their interiors [160,161]. In this way, these materials have potential applications for targeted removal of toxins or unwanted compounds, or also for drug delivery systems [125]. They could also be potentially used as catalytic materials. In some cases, the functional groups of the polymer lining the void spaces may also serve to facilitate binding between the host material and the target molecule. Liu and coworkers demonstrated that emulsification could be used to generate porous microspheres based on block copolymers such as PtBA-b-PCEMA or PI-b-PtBA (which were described earlier in Sections 2.3 and 2.4.1, respectively) after the subsequent hydrolysis of the PtBA block to yield PAA [94,98,162]. The interiors of these microspheres contained void channels which were lined with PAA domains that could bind to cations such as Cu2+ , Fe3+ , Mn2+ , and Pd2+ (Fig. 20). The void spaces among the PAA-bPCEMA microspheres arose from the loss of the tert-butyl group from the PtBA domains during the hydrolysis [94]. When PCEMA-b-PAA microspheres were stirred with an aqueous Pd(NO3 )2 solution, Liu and coworkers [162] determined that as much as 151 mg of Pd2+ could be incorporated into the PAA-lined channels per gram of microsphere. Furthermore, when they reduced the Pd2+ occupying the microspheres, the spheres became catalytically active, and could catalyze the hydrogenation of methyl methacrylate (MMA) to methyl 2-methylpropionate. The catalytic performance of the microspheres was compared with that of Pd black, and the conversion of MMA was more efficient

when the Pd-bearing spheres were used as catalysts than when Pd black was used. Porous PI-b-PAA microspheres were prepared in a similar manner [98]. In this case, the microspheres were prepared using a PI-b-PtBA/hPtBA blend. Consequently, hPAA could be removed after the hydrolysis step to yield larger void spaces within the spheres. In addition, the nature and size of the void regions and PAA domains could be tuned by adjusting the amount of hPtBA present during the emulsification (Fig. 21). Transition metals such as Fe3+ and Cu2+ could bind to the PAA-lined channels through the PAA carboxyl groups. Therefore, in addition to providing void spaces, these microspheres also directed metal loading through attractive interactions with the PAA domains. As mentioned earlier, the preparation of block copolymer microspheres through emulsification began with the work of Ogawa, for the purpose of preparing drug delivery systems [91]. The development of block copolymer-based drug delivery vehicles and biomedical devices has generated significant attention over the years, and has been described in numerous reviews [42,115,125,163–170]. While a variety of blocks are used, many of these systems utilize blocks such as PEG and PLA (or their derivatives) as hydrophilic and hydrophobic blocks, respectively [159]. Particles coated with PEG often have longer circulation times in living systems [110,125,171], due to the inhibited uptake of PEG-bearing nanoparticles by the reticulo-endothelial system (RES) [125]. This feature can allow PEG-coated particles to circulate long enough to deliver drugs to well-hidden targets, such as hard to reach tumors. As suggested above, a block-copolymer based delivery vehicle may enhance a drug’s effectiveness. For example, Onishi and coworkers [172] loaded the anti-tumor drug camptothecin into micelles of methoxypolyethylene glycol-block-poly(D,L-lactic acid) (MPEG-b-PLA) following an O/W emulsion. Both the copolymer and the drug were dissolved into the oil phase, which was composed of DCM. The PLA block collapsed as the DCM was subsequently evaporated, to form the resultant particle’s core,

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Fig. 18. Various images showing the influence of SDS concentration upon the morphologies of droplets containing PS-b-PEO. SEM images are shown in parts (a–c) and bright field TEM images are shown in images (d–f). When the SDS concentration was 0.1 mg/mL, spherical particles with rough surfaces were observed (a). Meanwhile, when the surfactant was increased to 0.5 (b) and 0.7 mg/mL (c) budding vesicles formed. The copolymer escaped from the droplets to form worm-like micelles of the copolymer when the SDS concentration was 1.0 mg/mL (d). A combination of worm-like and spherical micelles were observed when the concentration of SDS was 2.4 mg/mL (e). Predominantly spherical micelles formed when the concentration of SDS was increased to 5.0 mg/mL (f) [153]. Ref. [153]––Reproduced by permission of the Royal Society of Chemistry.

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Fig. 19. Bright field images of emulsion-droplets containing PLGA-b-PEO/hPLGA blends during the evaporation of dichloromethane. After approximately 1 h, PFOB begins to phase segregate from the rest of the oil phase, and becomes visible (second image from the left). The volume of the PFOB droplet increases during the evaporation process. Approximately 2.5 h after evaporation began, the surface of the droplet begins to roughen. This effect is enhanced with increasing weight fractions of the copolymer. The weight fractions of PLGA-b-PEO within the blend shown in the three images at the top right and bottom right are 5% and 100%, respectively [156]. Ref. [156]––Reproduced by permission of the Royal Society of Chemistry.

Fig. 20. TEM images of PCEMA-b-PtBA microspheres prior to Pd loading (a). Microspheres that have been loaded with 27% (b) and 63% (c) weight percentages of Pd are also shown [162]. Reprinted with permission from Reference [162]. Copyright 2001 American Chemical Society.

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Fig. 21. TEM images of spheres prepared from PI-b-PtBA/hPtBA blends after the hydrolysis of PtBA to PAA. The spheres on the left initially had a 32% volume fraction of PtBA (including both hPtBA and the PtBA block), while the spheres on the left initially had a 54% volume fraction of PtBA the blend. The samples were not stained, and the lighter regions represent void spaces remaining after hydrolysis of PtBA and extraction of PtBA. The darker regions correspond to the PI domains, the light grey regions correspond to PAA domains, while the white regions likely correspond to void spaces left after extraction of hPAA [98]. Reprinted with permission from Reference [98]. Copyright 2003 John Wiley and Sons.

while the MPEG blocks extended into the aqueous solution to form the corona. The hydrophobic effect helped direct the host–guest encapsulation, with camptothecin occupying the hydrophobic PLA domains of the particles. The activity of these particles against sarcoma 180 tumor cells was studied by injecting tumor-bearing mice with the camptothecin-loaded MPEG-b-PLA nanoparticles, and other mice with free solutions of the drug. The camptothecin was retained in the blood plasma for a longer duration among the mice injected with the nanoparticles than among those injected with free solutions of the drug. In addition, the volumes of the tumors in these mice decreased more dramatically compared with those injected with the free drug [172]. The confinement-induced self-assembly that is attained through emulsification provides a powerful means to prepare a variety of exotic structures. Choosing a block that can be readily modified so that it may consequently collapse or occupy a smaller volume, can yield particles with void spaces [94,162]. Larger void spaces may be obtained if a homopolymer is incorporated with the copolymer as a blend, especially if the homopolymer can be subsequently extracted from the particles [98]. In this scenario, the volume of the void spaces may be controlled by adjusting the homopolymer content. While the preparation of the block copolymer particles themselves are directed by conditions such as confinement, interfacial tension, or other phenomena, the incorporation of guest species into a host particle can also arise through directed assembly. This host–guest assembly may be driven by the hydrophobic effect, or other supramolecular activity such as hydrogen bonding, coordination bonding, electrostatic interactions, or ␲–␲ interactions. The block copolymer particle can act as a template to induce guest incorporation either within its interior or onto its surfaces through directed assembly. While these structures are often complex and fascinating in their own right, they also show very strong promise and utility for applications, such as for catalysts and drug delivery systems.

6. Perspectives and outlook The combination of block copolymer self-assembly and emulsification can provide a rich variety of morphologies and exciting applications. Complex architectures have been obtained both within the interiors of emulsion droplets, and also on droplet surfaces. A common paradigm followed for many preparations of block copolymer assemblies through emulsification is to dissolve the copolymer in a volatile organic solvent and mix this oil phase with an aqueous phase, which normally contains a surfactant to stabilize the emulsion droplets. These immiscible phases are then mixed together, normally by stirring or sonication, to form an emulsion. Organic solvent is then removed from the emulsion droplets via evaporation to induce collapse of at least one of the copolymer’s blocks, leading to assembly of the copolymer. Amphiphilic block copolymers are naturally well-adapted towards emulsification. In fact, their combination of hydrophilic and hydrophobic blocks allow them to behave as surfactants, thus sometimes allowing emulsion stabilization without requiring use of additional surfactant [119]. In addition, their amphiphilic nature can yield a variety of exotic morphologies through microphase segregation, depending on the prevailing conditions. 6.1. Microphase segregation within solid emulsion particles If both blocks collapse during solvent evaporation from an emulsion droplet, they may form the core of the resultant emulsion sphere and undergo microphase segregation. As seen in Section 2, there are a number of ways in which their morphology may be controlled. Since the blocks are confined within the emulsion sphere, D/L0 can play an important role on influencing the architecture [88,107]. As is the case in bulk, the volume fractions of the copolymer blocks is a major factor in determining the morphology of the copolymer assembly. A popular way to tune the morphology is through the use of copolymer/homopolymer

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blends. Adjusting the homopolymer content may have a similar effect as changing the block ratio of the copolymer, and may thus induce a morphological transition. As is the case in bulk, incremental changes of copolymer/homopolymer blend composition can allow one to fine tune the morphologies produced through emulsification [102]. Macrophase segregation may also occur in the presence of a homopolymer, particularly as its molecular weight becomes comparable with its corresponding blocks or if large amounts of homopolymer are present. Within emulsion spheres, a combination of these factors may influence the final morphology so that it will be unique from those observed either in bulk, or under a single influence. 6.2. Block copolymer vesicles through emulsification If the block copolymer assembles at the interface surrounding an emulsion droplet, and at least one of the blocks collapses upon solvent evaporation, the copolymer can form a vesicle. Water-filled polymersomes may be prepared if the copolymer is initially dissolved in the oil phase of a (W/O)/W double emulsion [123]. The inner aqueous droplet effectively serves as a template, with the copolymer behaving as a surfactant and assembling along the droplet surface, as well as at the interface between the oil phase and the surrounding aqueous solution as the organic solvent is removed. The use of microfluidic devices allows producion of monodisperse particles with easily controlled diameters. Alternatively, nanocapsules with oil-filled cores may be prepared by O/W emulsion [118]. The oil phase will often be a mixture of two organic solvents, one of which is volatile, and the other non-volatile. At least one of the blocks should be insoluble in the non-volatile solvent. Upon evaporation of the volatile solvent, the non-volatile solvent remains to form the oil-filled core of the capsule. The oilfilled core has a different composition than the surrounding solution. This feature differs from that of polymersomes, where both the vesicle core and the surrounding solution are aqueous media. In both cases, the inner droplet acts as a template for copolymer assembly. 6.3. Block copolymer assembly at 2D surfaces Block copolymer assembly may also occur on the surface of emulsion spheres with solid cores. The direction of these assemblies are quite similar to those involved in forming vesicles, with the block-copolymer assembly taking place at the interface between the surface of a droplet or a surface and the surrounding media. In contrast to double emulsions, this assembly normally occurs at one interface rather than two. However, hierarchical assembly may also be observed, such as the flower-like superaggregates and ribbon-cage structures reported by Liu and coworkers [141]. One may prepare particles with patchy or bumpy surfaces if two copolymers with similar hydrophobic blocks and different hydrophilic blocks assemble on an O/W droplet surface, and subsequently segregate themselves according to their hydrophilic block [140]. The surfactant may direct the assembly, even if it is not incorporated into the final assembly structure. If a surfactant is more compatible with one copolymer block than

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another, emulsion spheres with uniform surfaces result, with the choice of surfactant dictating the surface composition [142]. Alternatively, a mixture of surfactants, where each surfactant is more compatible with a different copolymer block, can yield particles with more than one of the blocks exposed to the surface, and may even produce nonspherical particles [143]. 6.4. Exotic and useful structures A diverse variety of block copolymer architectures are available through emulsification, some of which would be difficult or impossible to obtain through other approaches. The combination of directing influences that one may manipulate in block copolymer emulsification provides virtually endless possibilities. In addition to fascinating morphologies, emulsification can also yield block copolymer assemblies with various applications. In fact, emulsion particles derived from copolymers were first prepared by Ogawa et al. [91], for the purpose of developing drug delivery vehicles. Since that time, this has been a major area of research involving these particles. In addition to particles with solid cores, vesicles and polymersomes have attracted great interest as well [173]. Catalytic materials may be prepared through this route also, such as porous emulsion spheres [162]. Control of surface roughness via assembly of block copolymer surfactants [140], or by interfacial instability [146], provide promising routes towards developing catalytic surfaces. 6.5. Outlook Given the developments made in recent years, the potential for many further discoveries and applications to be developed in the future. Recent systematic studies [103,107,123,142,143,146] summarized in this review have furthered our understanding of block copolymer assembly occurring during the emulsification/solvent evaporation process, and how the assembly can be controlled. With this knowledge in hand, emulsification can provide a powerful method to tailor block copolymer architectures according to desired structures or applications. Many of the assembly systems described have been based on diblock copolymers, although triblock copolymers have used as well [118,130,141]. Given the greater morphological diversity of ABC triblock copolymers, their further use (as well as tetrablock and pentablock copolymers) in emulsification may generate highly complex assembly structures. Acknowledgements NSERC of Canada is gratefully acknowledged for funding this work. Guojun Liu wishes to thank the Canada Research Chair program for a senior Canada Research Chair position in Materials Science. References [1] Bates FS, Fredrickson GH. Block copolymers–designer soft materials. Phys Today 1999;52:32–8.

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[2] Ding J, Liu GJ. Polyisoprene-block-poly(2-cinnamoylethyl methacrylate) vesicles and their aggregates. Macromolecules 1997;30:655–7. [3] Yan X, Liu G, Li Z. Preparation and phase segregation of block copolymer nanotube multiblocks. J Am Chem Soc 2004;126:10059–66. [4] Khandpur AK, Forster S, Bates FS, Hamley IW, Ryan AJ, Bras W, Almdal K, Mortensen K. Polyisoprene-polystyrene diblock copolymer phase diagram near the order-disorder transition. Macromolecules 1995;28:8796–806. [5] Hamley IW. Block copolymers. Oxford: Oxford University Press; 1999. [6] Hasegawa H, Hashimoto T. Self-assembly and morphology of block copolymer systems. In: Allen G, Aggarwal SL, Russo S, editors. Comprehensive polymer science. Second supplement. London: Pergamon Press; 1996. p. 497–539. [7] Breiner U, Krappe U, Thomas EL, Stadler R. Structural characterization of the “knitting pattern” in polystyrene-block-poly(ethyleneco-butylene)-block-poly(methyl methacrylate) triblock copolymers. Macromolecules 1998;31:135–41. [8] Hajduk DA, Harper PE, Grunner SM, Honeker CC, Kim G, Thomas EL, Fetters LJ. The gyroid: a new equilibrium morphology in weakly segregated diblock copolymers. Macromolecules 1994;27:4063–75. [9] Hashimoto T, Kawamura T, Harada M, Tanaka H. Small-angle scattering from hexagonally packed cylindrical particles with paracrystalline distortion. Macromolecules 1994;27:3063–72. [10] Shefelbine TA, Vigild ME, Matsen MW, Hajduk DA, Hillourer MA, Cussler EL, Bates FS. Core-shell gyroid morphology in a poly(isoprene-block-styrene-block-dimethylsiloxane) triblock copolymer. J Am Chem Soc 1999;121:8457–65. [11] Breiner U, Krappe U, Abetz V, Stadler R. Cylindrical morphologies in asymmetric ABC triblock copolymers. Macromol Chem Phys 1997;198:1051–83. [12] Matsen MW, Schick M. Stable and unstable phases of a diblock copolymer melt. Phys Rev Lett 1994;72:2660–3. [13] Matsen MW, Schick M. Microphase separation in starblock copolymer melts. Macromolecules 1994;27:6761–7. [14] Matsen MW, Schick M. Stable and unstable phases of a linear multiblock copolymer melt. Macromolecules 1994;27:7157–63. [15] Leibler L. Theory of microphase separation in block copolymers. Macromolecules 1980;13:1602–17. [16] Helfand E, Wasserman ZR. Block copolymer theory. 4. Narrow interphase approximation. Macromolecules 1976;9:879–88. [17] Whitmore MD, Noolandi J. Self-consistent theory of block copolymer blends: neutral solvent. J Chem Phys 1990;93:2946–55. [18] Semenov AN. Contribution to the theory of microphase layering in block-copolymer melts. Sov Phys JETP 1985;61:733–42. [19] Qi S, Wang ZG. Kinetics of phase transitions in weakly segregated block copolymers: pseudostable and transient states. Phys Rev E 1997;55:1682–97. [20] Matsen MW, Bates FS. Unifying weak- and strong-segregation block copolymer theories. Macromolecules 1996;29:1091–8. [21] Cameron NS, Corbierre MK, Eisenberg A, Steacie EWR. Award Lecture: asymmetric amphiphilic block copolymers in solution: a morphological wonderland. Can J Chem 1999 1998;77:1311–26. [22] Zhang L, Eisenberg A. Multiple morphologies of “crew-cut” aggregates of polystyrene-b-poly(acrylic acid) block copolymers. Science 1995;268:1728–31. [23] Dupont J, Liu GJ, Niihara KI, Kimoto R, Jinnai H. Self-assembled ABC triblock copolymer double and triple helices. Angew Chem Int Ed 2009;48:6144–7. [24] Li Z, Liu GJ. Water-dispersible tetrablock copolymer synthesis, aggregation, nanotube preparation, and impregnation. Langmuir 2003;19:10480–6. [25] Gohy JF, Ott C, Hoeppener S, Schubert US. Multicompartment micelles from a metallo-supramolecular tetrablock quatercopolymer. Chem Commun 2009:6038–40. [26] Hoogenboom R, Wiesbrock F, Leenen MAM, Thijs HML, Huang H, Fustin CA, Guillet P, Gohy JF, Schubert US. Synthesis and aqueous micellization of amphiphilic tetrablock ter- and quarterpoly(2oxazoline)s. Macromolecules 2007;40:2837–43. [27] Fustin CA, Thijs-Lambermont HML, Hoeppener S, Hoogenboom R, Schubert US, Gohy JF. Multiple micellar morphologies from tri- and tetrablock copoly(2-oxazoline)s in binary water-ethanol mixtures. J Polym Sci Part A Polym Chem 2010;48:3095–102. [28] Takahashi K, Hasegawa H, Hashimoto T, Bellas V, Iatrou H, Hadjichristidis N. Four-phase triple coaxial cylindrical microdomain morphology in a linear tetrablock quaterpolymer of styrene, iso-

[29]

[30]

[31]

[32] [33]

[34]

[35]

[36]

[37]

[38]

[39]

[40]

[41]

[42]

[43]

[44]

[45]

[46]

[47] [48]

[49]

[50]

[51]

[52]

prene, dimethylsiloxane, and 2-vinylpyridine. Macromolecules 2002;35:4859–61. Kim HC, Park SM, Hinsberg W. Block copolymer based nanostructures: materials, processes, and applications to electronics. Chem Rev 2010;110:146–77. Thurn-Albrecht T, Schotter J, Kastle GA, Emley N, Shibauchi T, Krusin-Elbaum L, Guarini K, Black CT, Tuominen MT, Russell TP. Ultrahigh-density nanowire arrays grown in self-assembled diblock copolymer templates. Science 2000;290:2126–9. Massey JA, Winnik MA, Manners I, Chan VZH, Ostermann JM, Enchelmaier R, Spatz JP, Moller M. Fabrication of oriented nanoscopic ceramic lines from cylindrical micelles of an organometallic polyferrocene block copolymer. J Am Chem Soc 2001;123:3147–8. Liu GJ, Yan X, Li Z, Zhou J, Duncan S. End coupling of block copolymer nanotubes to nanospheres. J Am Chem Soc 2003;125:14039–45. Huang W, Kim JB, Baker GL, Bruening ML. Preparation of amphiphilic triblock copolymer brushes for surface patterning. Nanotechnology 2003;14:1075–80. Peng J, Xuan Y, Wang H, Yang Y, Li B, Han Y. Solventinduced microphase separation in diblock copolymer thin films with reversibly switchable morphology. J Chem Phys 2004;120:11163–70. Lazzari M, Scalarone D, Hoppe CE, Vazquez-Vazquez C, LopezQuintela MA. Tunable polyacrylonitrile-based micellar aggregates as a potential tool for the fabrication of carbon nanofibers. Chem Mater 2007;19:5818–20. Pietsch T, Gindy N, Mahltig B, Fahmi A. Fabrication of functional nano-objects via self-assembly of nanostructured hybrid materials. J Polym Sci Part B Polym Phys 2010;48:1642–50. Quemener D, Bonniol G, Phan TNT, Gigmes D, Bertin D, Deratani A. Free-standing nanomaterials from block copolymer self-assembly. Macromolecules 2010;43:5060–5. Li Z, Zhao W, Liu Y, Rafailovich MH, Sokolov J, Khougaz K, Eisenberg A, Lennox RB, Krausch G. Self-ordering of diblock copolymers from solution. J Am Chem Soc 1996;118:10892–3. Park M, Harrison C, Chaikin PM, Register RA, Adamson DH. Block copolymer lithography: periodic arrays of ∼1011 holes in 1 square centimeter. Science 1997;276:1401–4. Xu J, Park S, Wang S, Russell TP, Ocko BM, Checco A. Directed self-assembly of block copolymers on two-dimensional chemical patterns fabricated by electro-oxidation nanolithography. Adv Mater 2010;22:2268–72. Silva GA, Czeisler C, Niece KL, Beniash E, Harrington DA, Kessler JA, Stupp SI. Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science 2004;303:1352–5. Kataoka K, Harada A, Nagasaki Y. Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv Drug Delivery Rev 2001;47:113–31. Kabanov AV, Batrakova EA, Alakhov VY. Pluronic® block copolymers as novel therapeutics for drug and gene delivery. J Controlled Release 2002;82:189–212. Vriezema DM, Aragones MC, Elemans JAAW, Cornelissen JJLM, Rowan AE, Nolte RJM. Self-assembled nanoreactors. Chem Rev 2005;105:1445–89. Zhang L, Bartels C, Yu Y, Shen H, Eisenberg A. Mesosized crystallike structure of hexagonally packed hollow hoops by solution selfassembly of diblock copolymers. Phys Rev Lett 1997;79:5034–7. Ding JF, Liu GJ. Growth and morphology change of polystyrenemethacrylate) particles in block-poly(2-cinnamoylethyl solvent-nonsolvent mixtures before precipitation. Macromolecules 1999;32:8413–20. Darling SB. Directing the self-assembly of block copolymers. Prog Polym Sci 2007;32:1152–204. Elhadj S, Woody JW, Niu VS, Saraf RF. Orientation of selfassembled block copolymer cylinders perpendicular to electric field in mesoscale film. Appl Phys Lett 2003;82:871–3. Olszowka V, Hund M, Kuntermann V, Scherdel S, Tsarkova L, Boker A, Krausch G. Large scale alignment of a lamellar block copolymer thin film via electric fields: a time resolved SFM study. Soft Matter 2006;2:1089–94. Park S, Kim B, Xu J, Hofmann T, Ocko BM, Russell TP. Lateral ordering of cylindrical microdomains under solvent vapor. Macromolecules 2009;42:1278–84. Cheng JY, Ross CA, Smith HI, Thomas EL. Templated self-assembly of block copolymers: top-down helps bottom-up. Adv Mater 2006;18:2505–21. Li Z, Chen Z, Cui H, Hales K, Qi K, Wooley KL, Pochan DJ. Disk morphology and disk-to-cylinder tunability of poly(acrylic

I. Wyman et al. / Progress in Polymer Science 36 (2011) 1152–1183

[53]

[54] [55] [56] [57]

[58] [59] [60] [61] [62] [63] [64]

[65] [66] [67] [68] [69]

[70]

[71]

[72] [73]

[74]

[75]

[76]

[77]

[78]

[79]

[80]

[81]

acid)-b-poly(methyl acrylate)-b-polystyrene triblock copolymer solution-state assemblies. Langmuir 2005;21:7533–9. Hales K, Chen Z, Wooley KL, Pochan DJ. Nanoparticles with tunable internal structure from triblock copolymers of PAA-b-PMA-b-PS. Nano Lett 2008;7:2023–6. Bibette J, Calderon FL, Poulin P. Emulsions: basic principles. Rep Prog Phys 1999;62:969–1033. Friberg SE. Some emulsion features. J Dispersion Sci Technol 2007;28:1299–308. Leal-Calderon F, Thivilliers F, Schmitt V. Structured emulsions. Curr Opin Colloid Interface Sci 2007;12:206–12. Salager JL, Forgiarini A, Marquez L, Pena A, Pizzino A, Rodriguez MP, Rondon-Gonzalez M. Using emulsion inversion in industrial processes. Adv Colloid Interface Sci 2004;108–109:259–72. Schwuger MJ, Stickdorn K, Schomacker R. Microemulsions in technical processes. Chem Rev 1995;95:849–64. Solans C, Izquierdo P, Nolla J, Azemar N, Garcia-Celma MJ. Nanoemulsions. Curr Opin Colloid Interface Sci 2005;10:102–10. Matsen MW, Schick M. Self-assembly of block copolymers. Curr Opin Colloid Interface Sci 1996;1:329–36. Noolandi J, Shi AC. Self-assembly of block copolymers. Curr Opin Colloid Interface Sci 1998;3:436–9. Riess G. Micellization of block copolymers. Prog Polym Sci 2003;28:1107–70. Park C, Yoon J, Thomas EL. Enabling nanotechnology with self assembled block copolymer patterns. Polymer 2003;44:6725–60. Smart T, Lomas H, Massignani M, Flores-Merino MV, Perez LR, Battaglia G. Block copolymer nanostructures. Nano Today 2008;3:38–46. Kim JK, Yang SY, Lee Y, Kim Y. Functional nanomaterials based on block copolymer self-assembly. Prog Polym Sci 2010;35:1325–49. Grzelczak M, Vermant J, Furst EM, Liz-Marzan LM. Directing the self-assembly of nanoparticles. ACS Nano 2010;4:3591–605. Fasolka MJ, Mayes AM. Block copolymer thin films: physics and applications. Annu Rev Mater Res 2001;31:323–55. Hamley IW. Ordering in thin films of block copolymers: fundamentals to potential applications. Prog Polym Sci 2009;34:1161–210. Tsarkova L, Sevink GJA, Krausch G. Nanopattern evolution in block copolymer films: experiment, simulations and challenges. Adv Polym Sci 2010;227:33–73. Yu G, Cho W, Shin K. Polymers in nanotubes. In: Dunne LJ, Manos G, editors. Adsorption and phase behaviour in nanochannels and nanotubes. Dordrecht: Springer Science + Business Media B.V.; 2010. p. 101–19. Stewart-Sloan CR, Thomas EL. Interplay of symmetries of block copolymers and confining geometries. Eur Polym J 2011;47:630–46. Thomas EL, Reffner JR, Bellare J. A menagerie of interface structures in copolymer systems. J Phys Colloq 1990;51:c7363–74. Zhang K, Yu X, Gao L, Chen Y, Yang Z. Mesostructured spheres of organic/inorganic hybrid from gelable block copolymers and arched nano-objects thereof. Langmuir 2008;24:6542–8. Zhang K, Gao L, Chen Y, Yang Z. Onionlike spherical polymer composites with controlled dispersion of gold nanoclusters. Chem Mater 2008;20:23–5. Arsenault AC, Rider DA, Tetreault N, Chen JIL, Coombs N, Ozin GA, Manners I. Block copolymers under periodic, strong threedimensional confinement. J Am Chem Soc 2005;127:9954–5. Rider DA, Chen JIL, Eloi JC, Arsenault AC, Russell TP, Ozin GA, Manners I. Controlling the morphologies of organometallic block copolymers in the 3-dimensional spatial confinement of colloidal and inverse colloidal systems. Macromolecules 2008;41: 2250–9. Yabu H, Higuchi T, Shimomura M. Unique phase-separation structures of block copolymer nanoparticles. Adv Mater 2005;17:2062–5. Yabu H, Higuchi T, Ijiro K, Shimomura M. Spontaneous formation of polymer nanoparticles by good-solvent evaporation as a nonequilibrium process. Chaos 2005;15, 047505/1-7. Higuchi T, Tajima A, Motoyoshi K, Yabu H, Shimomura M. Frustrated phases of block copolymers in nanoparticles. Angew Chem Int Ed 2008;47:8044–6. Li L, Matsunaga K, Zhu J, Higuchi T, Yabu H, Shimomura M, Jinnai H, Hayward RC, Russell TP. Solvent-driven evolution of block copolymer morphology under 3D confinement. Macromolecules 2010;43:7807–12. Higuchi T, Tajima A, Yabu H, Shimomura M. Spontaneous formation of polymer nanoparticles with inner micro-phase separation structures. Soft Matter 2008;4:1302–5.

1181

[82] Yabu H, Motoyoshi K, Higuchi T, Shimomura M. Hierarchical structures in AB/BC type diblock-copolymer blend particles. Phys Chem Chem Phys 2010;12:11944–7. [83] Laidler KL, Meiser JH. Physical chemistry. 2nd Ed. Boston: Houghton Mifflin Company; 1995. pp. 862–863. [84] Xiang H, Shin K, Kim T, Moon S, McCarthy TJ, Russell TP. The influence of confinement and curvature on the morphology of block copolymers. J Polym Sci Part B Polym Phys 2005;43:3377–83. [85] He X, Song M, Liang H, Pan C. Self-assembly of the symmetric diblock copolymer in a confined state: Monte Carlo simulation. J Chem Phys 2001;114:10510–3. [86] Fraaije JGEM, Sevink GJA. Model for pattern formation in polymer surfactant nanodroplets. Macromolecules 2003;36:7891–3. [87] Feng J, Liu H, Hu Y. Microphase separation of diblock copolymer in a nanosphere: dissipative particle dynamics approach. Fluid Phase Equilib 2007;261:50–7. [88] Yu B, Li B, Jin Q, Ding D, Shi AC. Self-assembly of symmetric diblock copolymers confined in spherical nanopores. Macromolecules 2007;40:9133–42. [89] Chen P, Liang H, Shi AC. Microstructures of a cylinder-forming diblock copolymer under spherical confinement. Macromolecules 2008;41:8938–43. [90] Li S, Chen P, Zhang L, Liang H. Geometric frustration phases of diblock copolymers in nanoparticles. Langmuir 2011;27:5081–9. [91] Ogawa Y, Yamamoto M, Okada H, Yashiki T, Shimamoto T. A new technique to efficiently entrap leuprolide acetate into microcapsules of polylactic acid or copoly(lactic/glycolic acid). Chem Pharm Bull 1988;36:1095–103. [92] Vrancken MN. Process for encapsulating water and compounds in aqueous phase by evaporation. U.S. Patent 3,523,906; 1970. [93] Ouchi T, Hamada A, Ohya Y. Biodegradable microspheres having reactive groups prepared from L-lactic acid-depsipeptide copolymers. Macromol Chem Phys 1999;200:436–41. [94] Lu Z, Liu GJ, Liu F. Block copolymer microspheres containing intricate nanometer-sized segregation patterns. Macromolecules 2001;34:8814–7. [95] Liu GJ, Ding J, Hashimoto T, Kimishima K, Winnik FM, Nigam S. Thin films with densely, regularly packed nanochannels: preparation, characterization, and applications. Chem Mater 1999;11:2230–40. [96] Leibler L, Orland H, Wheeler JC. Theory of critical micelle concentration for solutions of block copolymers. J Chem Phys 1983;79:3550–7. [97] Ruzette AV, Leibler L. Block copolymers in tomorrow’s plastics. Nat Mater 2005;4:19–31. [98] Lu Z, Liu GJ, Liu F. Water-dispersible porous polyisoprene-blockpoly(acrylic acid) microspheres. J Appl Polym Sci 2003;90:2785–93. [99] Hashimoto T, Tanaka H, Hasegawa H. Ordered structure in mixtures of a block copolymer and homopolymers. 2. Effects of molecular weights of homopolymers. Macromolecules 1990;23:4378–86. [100] Tanaka H, Hasegawa H, Hashimoto T. Ordered structure in mixtures of a block copolymer and homopolymers. 1. Solubilization of low molecular weight homopolymers. Macromolecules 1991;24:240–51. [101] Winey KI, Thomas EL, Fetters LJ. Ordered morphologies in binary blends of diblock copolymer and homopolymer and characterization of their intermaterial dividing surfaces. J Chem Phys 1991;95:9367–75. [102] Okubo M, Saito N, Takekoh R, Kobayashi H. Morphology polystyrene/polystyrene-block-poly(methyl methacryof late)/poly(methyl methacrylate) composite particles. Polymer 2005;46:1151–6. [103] Tanaka T, Saito N, Okubo M. Control of layer thickness of onionlike multilayered composite polymer particles prepared by the solvent evaporation method. Macromolecules 2009;42:7423–9. [104] Hong KM, Noolandi J. Theory of phase equilibriums in systems containing block copolymers. Macromolecules 1983;16:1083–93. [105] Roe RJ, Zin WC. Phase equilibria and transition in mixtures of a homopolymer and a block copolymer. 2. Phase diagram. Macromolecules 1984;17:189–94. [106] Hashimoto H, Fujimora M, Hashimoto T, Kawai H. Domainboundary structure of styrene-isoprene block copolymer films cast from solutions. 7. Quantitative studies of solubilization of homopolymers in spherical domain systems. Macromolecules 1981;14:844–51. [107] Jeon SJ, Yi GR, Koo CM, Yang SM. Nanostructures inside colloidal particles of block copolymer/homopolymer blends. Macromolecules 2007;40:8430–9. [108] Matsen MW. Phase behavior of block copolymer/homopolymer blends. Macromolecules 1995;23:5765–73.

1182

I. Wyman et al. / Progress in Polymer Science 36 (2011) 1152–1183

[109] Dobriyal P, Xiang H, Kazuyuki M, Chen JT, Jinnai H, Russell TP. Cylindrical confined diblock copolymers. Macromolecules 2009;42:9082–8. [110] Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V, Langer R. Biodegradable long-circulating polymeric nanospheres. Science 1994;263:1600–3. [111] Blanazs A, Armes SP, Ryan AJ. Self-assembled block copolymer aggregates: from micelles to vesicles and their biological applications. Macromol Rapid Commun 2009;30:267–77. [112] Kita-Tokarczyk K, Grumelard J, Haefele T, Meier W. Block copolymer vesicles––using concepts from polymer chemistry to mimic biomembranes. Polymer 2005;46:3540–63. [113] Yow HN, Routh AF. Formation of liquid core-polymer shell microcapsules. Soft Matter 2006;2:940–9. [114] Discher DE, Ahmed F. Polymersomes. Annu Rev Biomed Eng 2006;8:323–41. [115] Mora-Huertas CE, Fessi H, Elaissari A. Polymer-based nanocapsules for drug delivery. Int J Pharm 2010;385:113–42. [116] Discher DE, Ortiz V, Srinivas G, Klein ML, Kim Y, Christian D, Cai S, Photos P, Ahmed F. Emerging applications of polymersomes in delivery: from molecular dynamics to shrinkage of tumors. Prog Polym Sci 2007;32:838–57. [117] Massignani M, Lomas H, Battaglia G. Polymersomes: a synthetic biological approach to encapsulation and delivery. Adv Polym Sci 2010;229:115–54. [118] Zheng R, Liu GJ. Water-dispersible oil-filled ABC triblock copolymer vesicles and nanochannels. Macromolecules 2007;40:5116–21. [119] Discher BM, Won YY, Ege DS, Lee JCM, Bates FS, Discher DE, Hammer DA. Polymersomes: tough vesicles made from diblock copolymers. Science 1999;284:1143–6. [120] Cho HK, Cheong IW, Lee JM, Kim JH. Polymeric nanoparticles, micelles and polymersomes from amphiphilic block copolymer. Korean J Chem Eng 2010;27:731–40. DE, Eisenberg A. Polymer vesicles. Science [121] Discher 2002;297:967–73. [122] Lorenceau E, Utada AS, Link DR, Cristobal G, Joanicot M, Weitz DA. Generation of polymersomes from double-emulsions. Langmuir 2005;21:9183–6. [123] Utada AS, Lorenceau E, Link DR, Kaplan PD, Stone HA, Weitz DA. Monodisperse double emulsions generated from a microcapillary device. Science 2005;308:537–41. [124] Hayward RC, Utada AS, Dan N, Weitz DA. Dewetting instability during the formation of polymersomes from block-copolymerstabilized double emulsions. Langmuir 2006;22:4457–61. [125] Letchford K, Burt H. A review of the formation of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes. Eur J Pharm Biopharm 2007;65:259–69. [126] Jain JP, Kumar N. Self assembly of amphiphilic (PEG)3 -PLA copolymer as polymersomes: preparation, characterization, and their evaluation as drug carrier. Biomacromolecules 2010;11:1027–35. [127] Ding J, Liu GJ. Water-soluble hollow nanospheres as potential drug carriers. J Phys Chem B 1998;102:6107–13. [128] Fallouh NAK, Roblot-Treupel L, Fessi H, Devissaguet JP, Puisieux F. Development of a new process for the manufacture of polyisobutylcyanoacrylate nanocapsules. Int J Pharm 1986;28:125–32. [129] Bae KH, Lee Y, Park TG. Oil-encapsulating PEO-PPO-PEO/PEG shell cross-linked nanocapsules for target-specific delivery of paclitaxel. Biomacromolecules 2007;8:650–6. [130] Shim JW, Kim SH, Jeon SJ, Yang SM, Yi GR. Microcapsules with tailored nanostructures by microphase separation of block copolymers. Chem Mater 2010;22:5593–600. [131] Huebner A, Sharma S, Srisa-Art M, Hollfelder F, Edel JB, deMello AJ. Microdroplets: a sea of applications? Lab Chip 2008;8:1244–54. [132] Seo M, Nie Z, Xu S, Mok M, Lewis PC, Graham R, Kumacheva E. Continuous microfluidic reactors for polymer particles. Langmuir 2005;21:11614–22. [133] Shum HC, Kim JW, Weitz DA. Microfluidic fabrication of monodisperse biocompatible and biodegradable polymersomes with controlled permeability. J Am Chem Soc 2008;130:9543–9. [134] Shum HC, Santanach-Carreras E, Kim JW, Ehrlicher A, Bibette J, Weitz DA. Dewetting-induced membrane formation by adhesion of amphiphile-laden devices. J Am Chem Soc 2011;133:4420–6. [135] Shum HC, Zhao YJ, Kim SH, Weitz DA. Multicompartment polymersomes from double emulsions. Angew Chem Int Ed 2011;50:1648–51. [136] Sun BJ, Shum HC, Holtze C, Weitz DA. Microfluidic melt emulsification for encapsulation and release of actives. ACS Appl Mater Interfaces 2010;2:3411–6.

[137] Shum HC, Abate AR, Lee D, Studart AR, Wang W, Chen CH, Thiele J, Shah RK, Krummel A, Weitz DA. Droplet microfluidics for fabrication of non-spherical particles. Macromol Rapid Commun 2010;31:108–18. [138] Thiele J, Abate AR, Shum HC, Bachtler S, Forster S, Weitz DA. Fabrication of polymersomes using double emulsion templates in glass-coated stamped microfluidic devices. Small 2010;6:1723–7. [139] Perro A, Nicolet C, Angly J, Lecommandoux S, Le Meins JF, Colin A. Mastering a double emulsion in a simple co-flow microfluidic to generate complex polymersomes. Langmuir 2011, online ASAP article, doi:10.1021/la1037102. [140] Zheng R, Liu GJ, Yan X. Polymer nano- and microspheres with bumpy and chain-segregated surfaces. J Am Chem Soc 2005;127:15358–9. [141] Hu J, Liu GJ, Nijkang G. Hierarchical interfacial assembly of ABC triblock copolymer. J Am Chem Soc 2008;130:3236–7. [142] Saito N, Takekoh R, Nakatsuru R, Okubo M. Effect of stabilizer on formation of “onionlike” multilayered polystyrene-block-poly(methyl methacrylate) particles. Langmuir 2007;23:5978–83. [143] Jeon SJ, Yi GR, Yang SM. Cooperative assembly of block copolymers with deformable interfaces: toward nanostructured particles. Adv Mater 2008;20:4103–8. [144] Fredrickson GH, Binder K. Kinetics of metastable states in block copolymer melts. J Chem Phys 1989;91:7265–75. [145] Sevink GJA, Zvelindovsky AV. Self-assembly of complex vesicles. Macromolecules 2005;38:7502–13. [146] Zhu J, Hayward RC. Spontaneous generation of amphiphilic block copolymer micelles with multiple morphologies through interfacial instabilities. J Am Chem Soc 2008;130:7496–502. [147] Zhu J, Hayward RC. Hierarchically structured microparticles formed by interfacial instabilities of emulsion droplets containing amphiphilic block copolymers. Angew Chem Int Ed 2008;47:2113–6. [148] Lopez-Montilla JC, Herrera-Morales PE, Pandey S, Shah DO. Spontaneuous emulsification: mechanisms, physicochemical aspects, modeling, and applications. J Dispersion Sci Technol 2002;23:219–68. [149] Lopez-Montilla JC, Herrera-Morales PE, Shah DO. New method to quantitatively determine the spontaneity of the emulsification process. Langmuir 2002;18:4258–62. [150] Hayward RC, Pochan DJ. Tailored assemblies of block copolymers in solution: it is all about the process. Macromolecules 2010;43:3577–84. [151] Geng Y, Discher DE. Hydrolytic degradation of poly(ethylene oxide)-block-polycaprolactone worm micelles. J Am Chem Soc 2005;127:12780–1. [152] Geng Y, Discher DE. Visualization of degradable worm micelle breakdown in relation to drug release. Polymer 2006;47:2519–25. [153] Zhu J, Ferrer N, Hayward RC. Tuning the assembly of amphiphilic block copolymers through instabilities of solvent/water interfaces in the presence of aqueous surfactants. Soft Matter 2009;5:2471–8. [154] Jain S, Bates FS. On the origins of morphological complexity in block copolymer surfactants. Science 2003;300:460–4. [155] Lee JCM, Bermudez H, Discher BM, Sheehan MA, Won YY, Bates FS, Discher DE. Preparation, stability, and in vitro performance of vesicles made with diblock copolymers. Biotechnol Bioeng 2001;73:135–45. [156] Pisani E, Ringard C, Nicolas V, Raphael E, Rosilio V, Moine L, Fattal E, Tsapis N. Tuning microcapsules surface morphology using blends of homo- and copolymers of PLGA and PLGA-PEG. Soft Matter 2009;5:3054–60. [157] Tomaszewski K, Szymanski A, Lukaszewski Z. Separation of poly(ethylene glycols) into fractions by sequential liquid-liquid extraction. Talanta 1999;50:299–306. [158] Malzert-Freon A, Benoit JP, Boury F. Interactions between poly(ethylene glycol) and protein in dichloromethane/water emulsions: a study of interfacial properties. Eur J Pharm Biopharm 2008;69:835–43. [159] Gref R, Quellec P, Sanchez A, Calvo P, Dellacherie E, Alonso MJ. Development and characterization of CyA-loaded poly(lactic acid)poly(ethylene glycol)PEG micro- and nanoparticles. Comparison with conventional PLA particulate carriers. Eur J Pharm Biopharm 2001;51:111–8. [160] Sellergren B, Allender CJ. Molecularly imprinted polymers: a bridge to advanced drug delivery. Adv Drug Delivery Rev 2005;57:1733–41. [161] Liu GJ, Zhou J. Diblock copolymer nanospheres with porous cores. 2. Porogen release and reuptake kinetics. Macromolecules 2002;35:8167–72.

I. Wyman et al. / Progress in Polymer Science 36 (2011) 1152–1183 [162] Lu Z, Liu GJ, Phillips H, Hill JM, Chang J, Kydd RA. Palladium nanoparticle catalyst prepared in poly(acrylic acid)-lined channels of diblock copolymer nanospheres. Nano Lett 2001;1:683–7. [163] Rosler A, Vandermeulen GWM, Klok HA. Advanced drug delivery devices via self-assembly of amphiphilic block copolymers. Adv Drug Delivery Rev 2001;53:95–108. [164] Lavasanifar A, Samuel J, Kwon GS. Poly(ethylene oxide)-blockpoly(L-amino acid) micelles for drug delivery. Adv Drug Delivery Rev 2002;54:169–90. [165] Harada A, Kataoka K. Supramolecular assemblies of block copolymers in aqueous media as nanocontainers relevant to biological applications. Prog Polym Sci 2006;31:949–82. [166] Sutton D, Nasongkla N, Blanco E, Gao J. Functionalized micellar systems for cancer targeted drug delivery. Pharm Res 2007;24:1029–46. [167] Batrakova EV, Kabanov AV. Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifers. J Controlled Release 2008;130:98–106.

1183

[168] Osada K, Christie RJ, Kataoka K. Polymeric micelles from poly(ethylene glycol)-poly(amino acid) block copolymer for drug and gene delivery. J R Soc Interface 2009;6:S325–39. [169] Tyrrell ZL, Shen Y, Radosz M. Fabrication of micellar nanoparticles for drug delivery through the self-assembly of block copolymers. Prog Polym Sci 2010;35:1128–43. [170] Oh JK. Polylactide (PLA)-based amphiphilic block copolymers: synthesis, self-assembly, and biomedical applications. Soft Matter 2011;7:5096–108. [171] Vonarbourg A, Passirani C, Saulnier P, Benoit JP. Parameters influencing the stealthiness of colloidal drug delivery systems. Biomaterials 2006;27:4356–73. [172] Miura H, Onishi H, Sasatsu M, Machida Y. Antitumor characteristics of methoxypolyethylene glycol-poly(DL-lactic acid) nanoparticles containing camptothecin. J Controlled Release 2004;97:101–3. [173] Meng F, Zhong Z, Feijen J. Stimuli-responsive polymersomes for programmed drug delivery. Biomacromolecules 2009;10: 197–209.