Equilibrium vesicles: fact or fiction?

ELSEVIER

Colloids and Surfaces A: Physicochemical and Engineering Aspects 128 ( 199-7)27 38

COLLOIDS AND SURFACES

A

Equilibrium vesicles: fact or fiction? R.G. Laughlin Miami Valley Laboratories, The Procter & Gamble Company, Cincinplati, OH 45253-8707. ~ S~4

Received 22 September 1996

Abstract Molecular aggregates of surfactant molecules consisting of one or more bilayers arranged in a hollow, closed, usually spherical geometry are termed "vesicles" or "liposomes". Often vesicles are formed by the application of intense mechanical shear to coarse dispersions of water-insoluble surfactants, in which case the thermodynamic state of the mixture evidently consists of the aqueous liquid plus a coexisting lamellar phase. In recent years it has been found that in certain systems the vesicular structure forms spontaneously and is longlived, and it has been suggested that these structures may in fact constitute the equilibrium state in these cases (as is true of micelles). It is here argued that vesicular mixtures are invariably biphasic, and that vesicular structure is to be regarded as a dimension of colloidal structure rather than of phase structure. If phase separation occurs when a cationic and an anionic surfactant are mixed in water, two new components result and diagnosis of the state of the mixture demands use of the rules governing five-component mixtures. By imposing the restriction that the surfactant in limiting quantity reacts irreversibly to form a catanionic surfactant salt, however, such mixtures may be rigorously treated as four-component systems. If the byproduct non-surfactant salt is removed, a manageable ternary system (catanionic surfactant, ionic surfactant, and waterj results. By taking this approach the thermodynamic state of these mixtures may be analyzed more simply and accurately, and a useful view of the physical science of vesicular mixtures results. © 1997 Published by Elsevier Science B.V. Keywords: Catanionic surfactants; Equilibrium; Phase behavior; Spontaneity; Thermodynamics; Vesicles

1. "Spontaneous" vesicle formation and vesicles as an "equilibrium" state The word "spontaneous" is defined in the 1986 Webster's Third New International Dictionary as (1) ~'caused by internal energy controlled and directed internally", or (2) "developing without apparent external influence of force". These definitions apply remarkably well to chemical phenomena, although real spontaneous processes display great diversity. While all such processes are accompanied by a decrease in free energy, some m o v e a mixture closer to its equilib-

rium state while others do not. The latter are governed by kinetic factors and activation free energies, and do not proceed directly towards equilibrium. Complexity of this nature reflects the existence of multiple free energy minima [ 1 ] . Indeed, it is generally true that "equilibrium" refers to the nearest accessible local m i n i m u m in free energy, within b o u n d a r y conditions imposed by kinetic barriers. In 1965 B a n g h a m discovered that the particles which exist within dilute aqueous mixtures of polar lipids have a roughly spherical shape and enclose part of the liquid phase [ 2 ] . Some are onion-like and possess m a n y layers encompassing an aqueous

0927-7757/97/$17.00 © 1997 Published by Elsevier Science B.V. All rights reserved PH S0927-7757( 97 )03899-X

28

R.G. Laughlin / Colloids" SurJaces A." Physicochem. Eng. Aspects 128 (1997) 27-38

core, while others possess only a single layer. From their size it was evident that these particles were aggregates of many molecules, and from other information it was apparent that the molecules within each layer were arranged in bilayers. Closed particles containing only one bilayer have been termed "unilamellar vesicles" (ULVs), while those containing many bilayers have been termed "multilamellar vesicles" (MLVs) [3]. The terms small ULVs and large ULVs have also been used. Alternatively, the term "liposome" has been used for many-bilayer particles and "vesicle" for singlebilayer particles; the latter terninology will be used in this paper. Vesicles, especially, have fascinated workers in this area. One reason is that in the radial direction the thickness of vesicle membranes is bimolecular (3-5 nm), and they may have similar dimensions and structures to the lipid fraction of living cell membranes [4 7]. Further, it is industrially important that the deposition and spreading of vesicles onto a surface results in more efficient coverage of the surface than the deposition of liposomes [8]. Within the last decade a theoretical concept [9-11] together with important new experimental observations [12-16] have conspired to suggest that vesicles may form "spontaneously", and may even constitute an "equilibrium" state. No one has suggested that this is universally true; it is generally agreed that many vesicular mixtures are biphasic dispersions of either a lamellar liquid crystal or a "gel" [17] phase (of ill-defined structure and composition) dispersed in an aqueous liquid. In selected systems, however, and in more and more papers in the recent literature [ 18-20], this new idea has been accepted as the truth. Since it is now generally agreed that micellar liquid solutions of surfactants are single phases [21], suggesting that "equilibrium vesicles" exist is tantamount to suggesting that micellar aggregates may assume a vesicular (hollow spherical) geometry. While the formation of vesicles may indeed occur spontaneously (in the sense that intense mechanical shear is not required), it is highly improbable that mixtures having vesicular structure ever constitute the true equilibrium state of a system. The objective of this paper is to collect and review the data and arguments which relate to this issue.

2. Discovery of vesicles and liposomes Do vesicular particles exist? Yes; the evidence that they do is unassailable. Abundant indirect evidence is supportive of their existence [4,5], but that provided by modern cryoelectron microscopy leaves virtually no doubt [22]. A very important caveat, however, is that closed spherical structures are not the only particle geometries which are assumed by vesicle-forming surfactants. Nonspherical closed structures, three-dimensional open structures, or flat sheets may also form (Fig. 1) [23]. Which geometry is found depends on the system and the history of a particular mixture. This fact alone suggests that vesicular structure is not a fundamental property of vesicle-forming molecules, in the sense that the equilibrium phase state is. It is of interest that non-amphiphilic compounds also tend to form hollow spherical aggregates under some circumstances. The thermal decomposition of aerosols of organometallic compounds yields hollow spherical particles [24]. The controlled hydrolysis of iron salts (to form colloidally dispersed iron oxide) at moderately acidic pH also yields hollow spherical aggregates [25].

3. What molecules form vesicles, and by what processes? Vesicles were discovered to form from surfactants that are strongly hydrophilic and have large lipophilic groups (for example, zwitterionic or ionic polar lipids). Many vesicle-forming surfactants have two (or more) long chains, and this structural feature has been strongly associated with the ability to form vesicles [8,9,26-29]. Extensive studies by Kunitake and coworkers have in the last several years established that vesicular structures may exist in aqueous dispersions of numerous multichain surfactants which contain a wide range of aliphatic, cyclic, and dipolar lipophilic groups [30,31]. Having two chains is not, however, a rigorous requirement for the formation of vesicles. Selected single-chain, weakly hydrophilic, surfactants also form vesicles [32,33], both alone and in mixtures with cholesterol. An example is C12Ea. Closely

R.G. Laughlin / Colloids Surfaces A. Physicochem. Eng. Aspects 128 (1997) 27 3~'

2~

Fig. 1. Cryolransmissionelectron micrographs of a dilute dioctadecyldimethylammoniummethyl sulfate dispersion showing la) nonspherical open structures, (b) simple flat sheets, and (c) a flat sheet probably having a curled edge.

related surfactants that do not by themselves form vesicles (e.g. C12Es) may be induced to do so by the addition of cholesterol. The early ideas about which elements of molecular structure favor vesicle formation need to be critically reviewed. As the chains of all such molecules are shortened, their solubility in liquid water increases. Dichain strongly hydrophilic homologs having Cs or C(, chains are water soluble and do not display surfactant phase behavior [34]. Homologs having a total of 16-20 carbon atoms are surfactants that have small but finite solubility, which progressively decreases as the chain length is increased. Rigorous determination of the equilibrium phase behavior of those compounds having intermediate chain lengths is particularly difficult, owing to their tendency to form complex, time-dependent colloidal structures. It is not surprising that the present controversy exists largely within this class of surfactants. Five basic processes ~each having many variants) have been discovered by means of which vesicular structure may be formed.

( 1 ) The application of intense mechanical shear to a liposomal dispersion of a fluid phase (usually a lamellar liquid crystal) within a dilute aqueous liquid phase is an important vesicle synthesis method. Shear may be imposed by sonication [35], by vortexing [33], or by forcing the dispersion through a tube, an orifice [36], or a membrane filter [37] under a high pressure drop. The dispersed phase cannot be crystalline, as crystals cannot be dispersed to colloidal dimensions even by intense sonication [38-40]. Vesicles result in this approach from the effect of brute mechanical shear on larger particles. Once formed at high temperatures, vesicle membranes may in selected compounds be "'frozen" into a "gel" state by lowering the temperature while retaining the vesicular structure. Since practically all crystalline surfactant phases have a bilayer structure ([41], pp. 184-1921, it is hardly surprising in retrospect that vesicular structure is not seriously disrupted by this process. (2t Precipitation from solution may yield vesicles. Dilution with water of a solution of the

30

R.G. Laughlin / Colloids Surj~tces A: Physicochem. Eng. Aspects 128 (1997) 27-38

surfactant in a water-miscible solvent [42], or the selective removal by dialysis of a soluble surfactant used to solubilize the vesicle-forming surfactant [43], may produce vesicles. Details of such processes strongly influence the size and other structural features of the resulting vesicles. Intense shear is not required, but the coupled use of shear plus dilution reduces the size and alters the size distribution of the vesicles formed. One may regard the initial stage of dilution as the creation of a metastable molecular solution, which collapses to yield particles of a colloidally dispersed precipitate which often (but not always) spontaneously assumes vesicular geometry. (3) Hydration of selected metastable crystal phases by heating coarse dispersions to appropriate temperatures [44,45] may yield vesicles. This process also occurs without intense shear, and does not occur when the equilibrium crystal phase is heated with water. It has been firmly established in the one known instance that providing nucleation sites yields a mixture of liquid plus macroscopic single-crystal phases [46]. (4) Deposition of a water-insoluble surfactant onto a wettable polar solid surface followed by immersion in water [47] yields vesicles. Wetting of the surface with displacement of adsorbed surfactant is the driving force for this process. (5) Finally, a chemical reaction which results in precipitation of the surfactant may produce vesicles. The acidification of a soap solution is one example [48]. The mixing of a water-soluble anionic surfactant with a water-soluble cationic surfactant within specific ranges of the molar ratio has been shown to result in vesicles [12-16]. Because this approach is both interesting academically and potentially important industrially, it serves well as a system with which to address the issues of spontaneous and equilibrium vesicles. All these approaches fall within two broad classes of methods. In one class vesicular particles are formed by the subdivision of larger particles, while in the other they are formed by the aggregation of individual molecules. Shearing apart a liquid crystalline particle and forming vesicles via the explosive disruption of a crystal due to osmotic pressure gradients are clearly subdivision processes. Forming vesicles by precipitation via dilu-

tion with a poor solvent, or by precipitation of an insoluble phase by a proton transfer or ion exchange chemical reaction, are examples of molecular aggregation.

4. The approach We will start by considering the phase behavior of spontaneous vesicle-forming systems, insofar as it is known. Once the equilibrium thermodynamic states that exist have been recognized, the rate of approach of non-equilibrium mixtures to equilibrium of state (at the phase structure level) will be considered. Finally, the colloidal science of biphasic mixtures will be addressed. These different aspects, taken together, constitute a comprehensive description of the physical science of spontaneous vesicleforming systems ([41], pp. 13-30).

5. Chemical processes in vesicle-forming systems The first step in any thermodynamic analysis is to define the system of interest. Ordinarily this is accomplished simply by stating the number of chemical compounds present and (for purpose of identification) their chemical structures. If no chemical interactions occur this process is straightforward, but if chemical reactions occur these must be taken into account ([41], pp. 14 17, 71-72, 103-104), because the value of C (the number of components present) in the phase rule changes. The phase rule equation is P + F = C + 2, where P is the number of phases and F is the number of degrees of freedom. (F is the number of thermodynamic variables whose magnitude must be specified in order to define the state.) Altering the value of C changes the value of P + F, and ignoring changes in C due to chemical reaction incurs serious risk of error. Proton transfer (acid-base) and ion exchange are the two most important chemical reactions that occur in surfactant systems ([41], pp. 14 17, 71 72, 103-104). Proton transfer is particularly important in weakly basic surfactants (such as soaps). Ion exchange (metathesis, double decomposition etc.) occurs only among salts. The ion

R. G. Laughlin/ColloMs Surfaces A: Physicochem. Eng. Aspects 128 (1997) 27 38

exchange reaction of particular interest is that which occurs between a water-soluble anionic surfactant M - R and a water-soluble cationic surfactant R +X : M+,R

+R~ X-~R+

R

+M+X

-

The products of this reaction are a "catanionic" surfactant, R+R , plus a non-surfactant salt, M+X . It has been recognized that this reaction probably proceeds essentially to completion for chain lengths of 12 or more carbon atoms [49], regardless of the physical state of the surfactant (liquid, liquid crystal, or crystal). The reaction is progressively less strongly favored as chain lengths decrease. Ion exchange processes which occur strictly in solution do not introduce new components. For example, a solution of sodium chloride and potassium bromide in water behaves as a strict ternary system. However, if the composition of one of the reaction products (e.g. sodium bromide) is independently varied, or if one of the two products (e.g. potassium chloride) separates from solution as a second phase, then two additional components are introduced and a five-component system exists. In mixtures of anionic and cationic surfactant salts the five components are the two ionic surfactant salts originally present, M+R and R+X - , the newly formed catanionic surfactant salt R+R , the non-surfactant salt M +X- , and water. Four-dimensional space is required to fully describe five-component phase data at constant temperature and pressure. While a fourdimensional figure may be manageable mathematically and within a computer, it cannot easily be visualized by the human mind. Arbitrary constraints must be applied in order to plot fivecomponent data, and these constraints preclude one from attaining the high level of intuitive analysis that is easily possible when viewing twocomponent composition-temperature plots (at constant pressure) or three-component isotherms (at constant temperature and pressure). Threedimensional space (e.g. a tetrahedron) is adequate to display four-component phase behavior at constant temperature and pressure, but the creation and visualization of a three-dimensional figure is, in fact, rarely attempted.

31

6. The thermodynamic-phase science aspects 6.1. Possible classes of systems The various surfactants that have been reported to form vesicles spontaneously have recently been reviewed by Kaler et al. [ 14] and are summarized in Table 1. If it may be assumed in the mixed anionic plus cationic systems that the catanionic surfactant is formed irreversibly [49], then a restraint on the dimensionality of the system is imposed. Simplification results because only four qualitatively different kinds of systems (Table 21 Table 1 Aqueous systems reported to form vesicles spontaneously [ 141] Reference

Type

System

[14]

Mixture of soluble catiomc and anionic surfactants

C8 to Cl( ,

[50]

[ 51 ]

Mixture of soluble cationic and anionic surfactants Mixture of soluble and insoluble cationic surfactants

[52]

Mixture of soluble and insoluble anionic surfactants

[48]

Soluble surfactant + amphiphilic oil Soluble surfactant + amphiphilic oil Soluble surfactant + amphiphilic oil Soluble surfactant + amphiphilic oil Mixture of soluble and insoluble zwitterionic surfactants Insoluble surfactant

[53] [54] [54] [55]

[56]

alkyltrimethylammonium tosylates or bromides + sodium dodecylbenzene sulfonate {commercial l, Cs to C~2 alkyl sulfates, or bem'ene sulfonate Alkyltrimethylammonium alkannates

Mixed alkylt rimethylammonium hydroxides (or acetates) and bromides Mixed sodium and choline salts of AOT {bis-2-ethylhexyl sulfosuccinatej Soap fatty acid mixtures kysolecithin fanv acid mixtures Soap fatly alcohol mixtures Soap cholesterol mixtures Lecilhin lysolecithin

A ganglioside (N-acylsphingosine polyglycoside)

32

R.G. Laughlin / Colloids" Surfaces A: Physicochem. Eng. Aspects 128 (1997) 2 ~ 3 8

Table 2 Systems possible in aqueous mixtures of anionic and cationic surfactants Compounds added (relative molar quantities)

Compounds actually present

Number C of phase rule components

M*R-,R+X -,H20

M*R ~, R+X , R~R , M+X , H20 R+R M+X -, HzO M+R ,R+R , M + X - , H 2 0 R+X ,R+R , M + X ,HzO

5

1M+R , 1R+X - , HzO > I M + R , 1R+X - , H z O 1M+R , > I R + X , H 2 0

,

may now exist. If M+R - and R+X are present in stoichiometrically equal amounts, the ternary system R + R - - M +X--water exists. If the anionic M +R- is in excess the quaternary system R+R M + R M+X -water exists, while if the cationic R+X - is in excess the quaternary system R+R R+X - M + X - - w a t e r exists. Both of these systems would be further simplified by removing the non-surfactant salt M+X -, which would yield manageable ternary systems. It is impossible to create the basic R+R--water binary system using this approach, as has been recognized by those workers who have troubled to remove this byproduct salt and to produce the pure catanionic surfactant salt [49].

6.2. Binary catanionic-water systems Understanding a ternary systems hinges on knowing the phase behavior of the three relevant binary systems, from which it may be inferred that a full understanding of a mixture of two ionic surfactants and water is not at present possible. The fundamental importance of the binary catanionic-water system was recognized by Jokela et al., who appear to have coined the term [49]. They also predicted (and demonstrated experimentally) that catanionic surfactants are poorly soluble in liquid water. It had earlier been found that catanionic surfactants are insoluble when the sum of the chain lengths exceeds 20 [56,57], and that (within reason) the distribution of methylene groups between the anion and the cation is immaterial. It was further established in this early study [49] that a Krafft eutectic exists when the catanionic is sufficiently crystalline. Below this eutectic temperature a crystal (dry or hydrated) coexists with the aqueous liquid phase, which is nearly

3 4 4

pure water. It would be desirable to determine AT (difference between melting point and Krafft eutectic temperature ([41], pp. 248-252)), but this appears not to have been done. The existing data raise the possibility that thermotropic liquid crystals exist in the dry unary systems [49].

6.3. Ternary catanionic soluble surfactant--water systems The phase diagrams of several catanioni~soluble ionic surfactant-water systems have been investigated using nuclear magnetic resonance (NMR) methods. The phase behavior observed is strongly reminiscent of that of the lecithin-CTAB-water (where CTAB is cetyltrimethylammonium bromide, n-C16H33N+(CH3)3,Br - ) system studied earlier by Rydhag and Gabr~in (Fig. 2) [59]. In all these diagrams the two edges of the triangle connected to the water vertex display qualitatively different phase behavior, which requires that at least one phase boundary lie between them. Along the R +R--water border biphasic mixtures exist, while along the soluble surfactant-water border the micellar liquid phase extends from the water vertex to the liquid crystal solubility boundary, which is typically a hexagonal phase boundary [60]. The data show that R +R- is miscible with this micellar liquid phase, as the micellar region extends into the triangle a finite distance. The separating phase beyond the limit of miscibility of R+R - with the micellar solution is the lamellar liquid crystal that is formed by binary aqueous mixtures of R +R-. The data also show that the soluble surfactant is miscible with the R+R liquid crystal, as this region too extends into the triangle. Other phases are formed in mixtures having a lower water

R.G. Laughlin ," Colloids" Surfaces A: Physicochem. Eng..4spect.~ 128 (1997) 27 36'

33

DSPC

DMPC

,\

/

/

\

\\

/

\

\,

4o /

\~ 60

\\

Liq +\D

LIQ - L a m ( D ~

,::~' \,

;~Lam (D) ,,

m \

2O

\ \ 20

. - / . - Liq + D

\

LIQUid

\

e

V \\

H20

r

"i>

/ Hex(E)

20

:,

40

:"

7"-60

/

H20

\,

,.

CTAB

Fig. 2. Partial phase diagram of the dimyristoylphosphatidyl choline (DMPCJ-CTAB-water system at 30°C showing the extensive swelling of the lamellar liquid crystal phase and extensive solubilization of D M P C within the micellar liquid region of CTAB. Data taken from [41], pp. 165 176.

composition beyond those compositions of immediate concern with respect to vesicle formation. Rydhag and Gabrfin found that dissolution of CTAB in the lamellar liquid crystal of dimyristoyl lecithin ( D M P C ) dramatically increases the range of water compositions within which this phase exists [59]. Whereas the water composition of the phase in the absence of CTAB is 40%, at a ratio of CTAB to D M P C of 0.3 to 0.4 it is about 99%. Thus, the number of molecules of water per surfactant molecule at the limit of swelling increases from about 56 to 4000 in the presence of CTAB. At the same time, D M P C is incorporated into the micellar solution phase of CTAB at a weight percentage that is about equal to the CTAB present, at water compositions above 55%. The more recent studies of ternary catanionic-soluble i o n i ~ water systems [61] show that qualitatively similar behavior exists in these systems. Although a phase study was not performed, data on the solubilization of distearoylphosphatidyl choline (DSPC, C 1 7 H 3 5 C O 2 C H z ( C 1 7 H 3 5 C O 2 ) CHCH2OPO2OCH 2 CHzN+(CH3)3) vesicles by soluble surfactants are fully consistent with these results (Fig. 3) [62]. Solubilization data were determined for various ammoniohexanoate surfac-

zo

.,,

~,

C14AH

mg/I C,.AH Fig. 3. The dilute aqueous corner of tile DSPC6-hexadecyldimethylammoniohexanoate (C~4AH)-water phase diagram at 6 0 C, showing the limit of existence of the liquid phase boundary. The intercept with the abscissa (the onset of solubilization) is 3.03 x 10 ~ M, which is equal to (t.77 of the CMC. The solubilization efficiency is 1.01 g D S P C g Cu,AH Data taken from [62].

tants by titrating a vesicular dispersion of DSPC into solutions of the surfactant. Equilibrium was rapidly attained when the soluble surfactant was in excess during the titration, while it was not attained after many hours when the vesicles were in excess. The experiment was followed by light scattering using a Sofica instrument. Scattering intensities were shown to be a precise linear function of the vesicle particle number concentration, in the absence of the soluble surfactant. This method allows one to determine accurately the boundary of the liquid phase region at extremely low concentrations, as shown in Fig. 3. (It is worth noting that this figure spans only 1 part in 10~ of the total area of the phase diagram.) The onset of solubilization occurs just below the critical micellar concentration (CMC) of the surfactants (0.77 of the CMC in the C14 homologt. Within a finite range of compositions, the solubilization efficiency ( D S P C : A H ratio) is constant. Its value depends on the chain length of the AH: the maximum ratio (by weightl of DSPC to AH in the saturated solution was found at the matching chain lengths. It was observed during this work that the scattering intensity of the coexisting particles was signifi-

34

R.G. Laughlin / Colloids Surfaces A. Physicochem. Eng. Aspects 128 (1997) 27-38

cantly lowered (by a factor of about 3) in the presence of the AH. The latter result, especially, is consistent with the hypothesis that the swelling of the dispersed DSPC particles by water is increased by the presence of AH, just as was found by Rydhag and Gabrfin in the CTAB-lecithin study. The theoretical analysis based on electrostatic forces used by these workers to explain their results cannot apply to AH surfactants, however, as AHs are nonionic surfactants.

7. Kinetics of phase equilibration Highly swollen water-rich liquid crystal phases may be assumed to attain their equilibrium phase compositions and structures very fast. If vesicular particles having liquid crystalline membranes are cooled to below the Krafft eutectic temperature, however, supercooling can be expected ([41], pp. 155-163). It seems likely that the molecules present will be "frozen" by cooling into a disordered but solid-like state which, while far from equilibrium, may persist for long periods of time. In D O D M A C vesicles it was shown, using IR frequency data, that the conformational structure of the chains below the Krafft eutectic was much less disordered than those found in fluid phases but significantly different from that found in the equilibrium crystal [45]. In the DODMAC-water system, vesicular particles at temperatures below the Krafft eutectic were found to collapse to well-formed single crystals of substantial size and minimal curvature if nucleation sites were provided (Fig. 4) [46]. This result demonstrates that both the equilibration of phase structure and the collapse of colloidal structure are accelerated by the presence of nucleation sites.

8. Colloidal aspects The phase behavior of catanionic systems has a strong bearing on colloidal phenomena. A parameter which influences many colloidal phenomena is the mass or volume fraction of the phases present, and increasing the hydration level of a coexisting

Fig. 4. Electron micrograph of the crystalline particles which separated from a vesicular dispersion of DODMAC. This micrograph shows that colloidal structure has collapsed and single crystals have formed, but the actual crystal is the nonequilibrium X.W monohydrate, not the equilibrium X.W 2 dihydrate. Arrows point to multibilayer terraces. Reproduced with permission from the American Chemical Society, Journal of Physical Chemistry, 96 (1992) 380, Fig. 11.

phase increases the fraction of this phase. A waterrich liquid crystal which is subdivided and arranged into vesicular geometry occupies a much larger volume fraction of the mixture than would be expected from consideration of phase compositions, because of inclusion of the core volume. For this reason, vesicular dispersions may require a far higher rheological stress to induce a given strain than the volume fraction of the dispersed phase would suggest. It is for this reason that such mixtures are often viewed as being "gels", although in the structural use of the word they are in fact "sols" [46]. Vesicle gels are composed of discrete particles which interact very strongly with one another. Concentrated lamellar phases are intrinsically highly viscous, while dilute water-rich phases have very low viscosities. Quantitative rheological studies of the lamellar phase of a catanionic surfactant or of D O D M A C have not been reported, but qualitative evidence clearly indicates that the viscosity of the dilute D O D M A C phase is very low. This phase may easily be forced at temperatures near the Krafft eutectic through a 0.7 mm diameter orifice that is 2.5 cm long, while the concentrated phase may not [-45]. Because the mole fractions of water in the aque-

R.G. Laughlin / Colloids" Surfaces A. Physicochem. Eng. Aspects 128 (1997) 27 3~'

ous liquid phase and the swollen lamellar phase are very high, the water contribution to the free energy of both these phases is also very high ([-41], pp. 165 176). It may therefore also be expected that interfacial tensions at the liquid-liquid crystal interface will be low (relative to the tensions at the aqueous interface with concentrated phases). These various factors taken together suggest that the subdivision of a dilute liquid crystal within an aqueous liquid phase should be very easy, and also that the driving force for the collapse of this colloidal structure should be very small. The opposite situation should result if the liquid crystal is very concentrated; large differences in thermodynamic and other properties may be expected to exist, interfacial tensions should be relatively high, phase viscosities should also be high (as is found), and the formation of colloidal structure should be difficult. The observed differences in swelling behavior between systems for which the coexisting liquid crystal is dilute vs. those for which the coexisting phase is concentrated provide support for these hypotheses. Swelling information is obtained during diffusive interfacial transport phase studies, in which an interface between a surfactant and water is created within a thin rectangular cross-section capillary [63]. When a concentrated liquid crystal phase coexists with an aqueous liquid phase, normal swelling is observed. Clean interfaces result, and smooth composition profiles extend from this interface in both directions. An example of this behavior is found in both the D O D M A C [-45] and the DOACS-water (where DOACS is dioctadecylammonium cumenesulfonate, (C18H37)z+NH2, C3HvC~,H4SO3,Na +) system (shown in Fig. 5) [-64]. When the coexisting liquid crystal is dilute, however, relaxation of the initial non-equilibrium state does not occur by molecular diffusion. Instead, the intrusion of bulk liquid water into the liquid crystal phase creates a complex, macroscopic, geometric (myelinic) texture within the interfacial region of the cell [-45]. This behavior was first discovered in polar lipid-water systems, but is also a characteristic of di-long-chain quaternary ammonium salt surfactants. It is not restricted to di-long-chain surfactants, as any surfactant

35 I

150

Liq

+

Liq

Liquid

l

I

125

"11 1

Dq + D

100

Lam iqDI

d 75

X ~ 5o

....

Tt i!

25

Liq + X W

,~

xw

!i I

0

• i

Ice+XW 0

10

20

30

40

50

60

70

80

90

100

Percent D O A C S

Fig. 5. The phase diagram of the dioctadecylammonium cumcnesulfonate (DOACSFwater system. The maximum extent of swelling of the lamellar liquid crystal phase (6% 7%) is remarkably small in comparison with that of D O D M A C {69%). Myelinic texture does not form from DOACS during swelling studies.

which shows the correct phase behavior has so far been found to form myelinic texture and display anomalous swelling [-65]. Finally, this texture is not observed if any other kind of phase behavior exists. Both kinds of swelling behavior are seen in the C12E3 water system. Below 39~C (where the coexisting phase is lamellar liquid crystal) the swelling of this surfactant is anomalous, while above this temperature (where the coexisting phase is the sponge or L 3 liquid phase) it is normal.

9. Summary Vesicular aqueous mixtures of DODMAC at temperatures below the Krafft eutectic temperature collapse (if nucleation is provided) to form single crystals. This proves unambiguously both that these vesicles constitute a non-equilibrium phase state, and that vesicular structure is a form of irreversible colloidal structure at room temperature. All other existing data on this system are consistent with this premise. At temperatures above the Krafft eutectic, the firmly established equilibrium phase behavior of D O D M A C suggests that the vesicle membranes should swell by incorporation of water, to form a hydrated membrane having a lamellar liquid-crystal-like composition and structure. It is improbable that vesicular geometry

36

R.G. Laughlin / Colloids Surfaces A: Physicochem. Eng. Aspects 128 (1997) 2 ~ 3 8

is an equilibrium state at one temperature and not at another, and it is reasonable to assume that vesicular mixtures having disordered membranes do not constitute equilibrium states. In bicontinuous phases an equilibrium phase is divided into two discrete regions separated by a network of the amphiphilic molecules, but the fraction of these two regions is reproducible and history-independent. In vesicular mixtures this fraction is neither reproducible nor history-independent. Moreover, the magnitude of the interracial regions separating the core and continuous regions is also history-dependent in vesicular mixtures. Typically coexisting phases in equilibrium are space filling, continuous, and assume a form in which interracial area (and therefore energy) is minimized, but these are not features of vesicular mixtures. Vesicles have to date been formed only in those systems and under those conditions in which an aqueous liquid phase coexists with a lamellar liquid crystal phase. Insofar as is known, no other coexisting liquid crystal phase can be dispersed to form vesicular aggregates. When the coexisting phase is a crystal, for example, they cannot be formed by subdivision, even using intense sonication. The available data suggest that the details of molecular structure (such as its geometric features) are inconsequential with respect to vesicle formation so long as the correct phase behavior exists. Phase behavior is influenced not only by molecular structure (including molecular geometry), but also by the magnitudes of the system variables (composition, temperature, pressure). The geometric aspect of molecules is very important, but it is only one of several parameters which influence phase behavior and, by inference, vesicle formation. A vesicle may be viewed as a fragment of the bilayer of a bulk liquid crystal (or crystal) phase that has been formed into a closed spherical shape. Their creation by the precipitation of surfactant molecules (by dilution or ion exchange reactions) indicates that this aggregate geometry is strongly favored kinetically. The bilayer that exists in a vesicle is likely to be quantitatively distorted from its equilibrium structure, energy, and composition, but these properties of the equilibrium bulk phase

must not be ignored in considering the actual composition and structure of vesicles. There is a great need in this area ( 1) to determine using unambiguous methods the equilibrium phase diagram of spontaneous vesicle-forming systems in well-defined systems of manageable complexity, and (2) to discern experimentally the extent and nature of the distortion of this membrane from its parent equilibrium phase composition and structure. The equilibrium state, in this approach, constitutes a well-defined point of reference for such analyses. The colloid science of vesicles must accommodate the fact that they are not constructed from a rigid phase which is dry and lies more than 500°C below its melting point (as is the case with silver iodide). They are constructed from highly hydrated phases of swelling amphiphiles which are held together by weak intermolecular forces (compared with those within inorganic solids). These phases contain a lot of water, and they undergo both smooth and discontinuous changes of state as temperature is varied. Finally, it may be noted that the temptation to incorporate the analysis of colloidal structure within the framework of classical thermodynamics is an old idea that is constantly reappearing in new guises ([41], pp. 88 89). The present interest in vesicles as equilibrium states may be regarded as a continuation of this tendency. The reasons for continuing interest in this subject are mystifying, as by doing so the classical, very well-established, and extremely useful laws of chemical thermodynamics are compromised. Experience in surfactant science has shown that fewer mistakes result if the thermodynamic aspects of physical science are viewed separately from the colloidal aspects, both being very important. In the present instance, what motivation exists for pursuing rigorous determination of the equilibrium phase diagram of such systems if vesicles are accepted as equilibrium states? Progress in the physical science of these systems will be more rapid if this temptation is resisted.

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