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Mechanism of the temperature-responsive material regulating porous morphology on epoxy phenolic novolac resin microcapsule surface
Colloids and Surfaces A 593 (2020) 124581
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Mechanism of the temperature-responsive material regulating porous morphology on epoxy phenolic novolac resin microcapsule surface
T
Xianpeng Zhanga, Luxia Zhangb, Daxia Zhangc, Sisi Liub,*, Dengguo Weib,*, Feng Liuc,* a
College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, PR China College of Science, Huazhong Agricultural University, Wuhan, Hubei, 430070, PR China c Key Laboratory of Pesticide Toxicology & Application Technique, Shandong Agricultural University, Tai’an, Shandong, 271018, PR China b
GRAPHICAL ABSTRACT
ARTICLE INFO
ABSTRACT
Keywords: Surface porous microcapsules Tunable pore size Temperature effect Pore formation mechanism
Porous microcapsules (MCs) with tailorable surface morphology are indispensable in practical applications because of their large surface area and controlled release. In this study, epoxy phenolic novolac resin MCs were prepared with temperature-responsive 2,4,6-tris(dimethylaminomethyl)phenol (DMP) as crosslinker. Reaction temperature was proved to generate distinct effects on MC porous morphology, shell thickness, mechanical strength and release behavior. The MC surface varied from nonporous to dense small pores (ca. 237 nm in diameter) with increasing temperature from 40 °C to 70 °C, but they showed decreasing tendency at higher temperature (＞70 °C). The encapsulation process illuminated that DMP aggregates formed and deposited on the loose shells at 60 °C and 70 °C (close to the so-called cloud point (Tscp) of DMP), leading to porous morphology. Nevertheless, at temperature far below or above the Tscp of DMP (＜50 °C or ＞70 °C), DMP kept its solubility in water or insufficiently deposited on the shells, which resulted in no pores existed. Higher temperature promoted the reactivity to generate thicker shells and larger mechanical strength, further leading to prolong payload release. The present work provided an insight about the reaction temperature to prepare tunable MCs, which can be employed to encapsulate lipophilic components in agriculture field.
1. Introduction Microcapsules (MCs) containing various active substances pose
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immense advantages in a wide range of applications, including drug delivery, self-healing materials, environmental engineering and industrial applications [1–6]. One of the most prominent characteristics
Corresponding authors. E-mail addresses: [email protected] (S. Liu), [email protected] (D. Wei), [email protected] (F. Liu).
https://doi.org/10.1016/j.colsurfa.2020.124581 Received 9 January 2020; Received in revised form 6 February 2020; Accepted 10 February 2020 Available online 11 February 2020 0927-7757/ © 2020 Elsevier B.V. All rights reserved.
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of MCs is their controlled release, which can be easily tailored by varying the microstructure of the capsule shells [7–9]. Porous MCs are known to have large specific surface area and confined inner space, and have been extended to fit different applications as needed [10–12]. Nowadays, porous MCs with tunable pore size and pore density have become a research hotspot because of their versatility and universality [13,14]. Along with the development of microencapsulation technique in recent years, MCs with precisely tailoring structures in the micrometer/ nanometer region are highly promising owing to the possibility to achieve core delivery on demand [15,16]. The key element for the preparation of smart payload carriers depends on the shell structures [17]. Some researcher commitment to modify the capsule shells via a chemical or physical change that can be triggered by external stimulus, such as pH, temperature, ultrasound, or light [18–21]; based on such mechanism, the cargo release from MCs is either in an “ON” state or in an “OFF” state, this also results in complex architecture and synthesis of MCs [22]. Others focused on physical response release that induced physical changes to the capsule structures, such as surface morphology, mechanical strength, thickness, pore size, etc [23–27]. Comparably, it is easier to fabricate MCs with tunable profile by varying suitable fabrication parameters. In addition, the synthesis of MCs is a complex procedure due to the complicated compositions and diversiform reaction conditions. The differences in operating parameters largely determine the physicochemical properties of as-prepared MCs, which are essential for their practical applications [28,29]. Among these operating parameters, reparation temperature can exert a vital influence on capsule properties, since it affects the material solubility, phase change behavior and reactivity, etc [30–33]. Therefore, it is required that the operating conditions should be precisely governed to guarantee the controllable structure and profile of MCs. Recently, we successfully prepared porous MCs with tunable pore size by regulating the amount of crosslinker, ratio of core material to shell or epoxy value of wallforming material [13,34]. Additionally, the influence of operating temperature was important for the synthesis of such porous MCs, in which changing reaction temperature could markedly affect the phase change behavior and solubility of the crosslinker, and further determined the final morphology of MCs. Detailed investigation on temperature effect will not only give theoretical understand, but may also offer the route to accurately prepare porous MCs. Therefore, the mechanism needs to be further confirmed with a wider range of reaction temperature. Moreover, the physicochemical properties and poreforming mechanism of such MCs based on reaction temperature have not been thoroughly studied. Pendimethalin (N-(l-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzenamine) is a dinitroaniline herbicide used for the control annual grasses and broadleaf weeds. However, pendimethalin has high toxicity to aquatic organisms; the emulsifiable concentrate is most widely used formulation due to its inferior water solubility (0.3 mg/L at 20 °C), all of which lead to toxicity risks and environmental pollution [35,36]. The controlled release technology has been highly desirable and emerged as an alternative approach. We thus chose pendimethalin as a model payload to solve the possible negative effects and improve its utilization. In the present study, epoxy phenolic novolac resin-based MCs (EPNMCs) were fabricated using 2,4,6-tris(dimethylaminomethyl)phenol (DMP, a temperature-responsive material with the so-called cloud point (Tscp) of 61 ± 3 °C) as crosslinker at temperatures both above and below its Tscp. The effects of temperature on the surface morphology, pore size, and particle size as well as thickness, mechanical strength and release behavior were systematically investigated. This work provided an insight on the reaction temperature to prepare porous MCs with tunable surface morphology, which has potential applications in lipophilic functional component encapsulation for controlled release in agriculture field.
Fig. 1. SEM image of porous MCs prepared using DMP as crosslinker at 60 °C. The inset is the high-magnification image.
2. Materials and methods 2.1. Materials Epoxy phenolic novolac resin (EPN), with epoxy value of 0.46 mol per 100 g, was purchased from Shanghai Resin Plant, China. 2,4,6-tris (dimethylaminomethyl)phenol (DMP), used as a crosslinker, was purchased from Sigma-Aldrich Chemical Co. (Shanghai, China). Pendimethalin (purity 99 %), used as a model core, was purchased from Sigma-Aldrich Chemical Co. (Shanghai, China). Polyoxyethylene sorbitan monooleate (Tween-80) was used as surfactant. All other reagents were of analytical grade and used without further purification. Deionized water was used in all experiments. 2.2. Preparation of microcapsules EPN-MCs were prepared by an interfacial emulsion polymerization technique according to previously reported methods [13]. Briefly, the oil phase consisted of pendimethalin and wall-forming material was obtained by dissolving pendimethalin (12 g) and EPN (3 g) in xylene (4 mL). The aqueous phase consisted of surfactant was obtained by dissolving Tween-80 (1.2 g) in deionized water (75 mL). The oil phase was dispersed in aqueous phase and homogenized at 10,000 rpm for 120 s with a homogenizer (IKA T18, Digital ULTRA-TURRAX, Germany) to generate a stable oil-in-water (O/W) emulsion. Subsequently, the homogeneous emulsion was poured into a three-necked round-bottom flask equipped with a water thermostat bath and mechanical stirrer. The system was heated to certain temperature (ranging from 40 °C to 90 °C), and then, DMP solution (0.18 g of DMP dissolved in 3.5 mL deionized water) was added dropwise to the system under constant stirring at 300 rpm. The polymerization reaction proceeded for 5 h to obtain core-shell-structured MCs. At last, the reaction system was cooled down to room temperature, the microcapsules were washed with deionized water and then dried in a vacuum oven at 40 °C for 72 h. 2.3. Preparation of microcapsule shells The microcapsule shells were obtained by removing the payload core. Briefly, a given amount of pendimethalin-loaded MCs was dissolved in 5 mL of methanol, and then the solution was ultrasonicated for 2 h to break the capsule shells. Subsequently, the mixture was centrifuged at 10,000 rpm and the supernatant was discarded. The precipitate was washed with methanol and deionized water successively, and then, dried in a vacuum oven at 40 °C for 4 h. 2
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Fig. 2. SEM images of MCs prepared by changing the reaction temperatures: (A) 40 °C, (B) 50 °C, (C) 70 °C, (D) 80 °C and (E) 90 °C, and (F) pore diameter of MCs prepared at different reaction temperatures.
(0.5 g was dissolved in hexane 50 mL, and then the system was disrupted with ultrasound for 2 h to ensure the complete burst of the MC samples. The mixture was centrifuged at 10,000 rpm and the supernatant was collected. The pendimethalin concentration in the supernatant was measured by UV detector at a wavelength of 238 nm. The mobile phase of the HPLC system was composed of methanol and water (90:10, v/v) at a flow rate of 1 mL/min. The column temperature was room temperature. The encapsulation efficiency and drug loading content were calculated using the following Equation: Encapsulation efficiency = (mass of pendimethalin in MC particles/ total mass of pendimethalin used for the MC particles preparation) × 100 % Drug loading content = (mass of pendimethalin in MC particles/total mass of MC particles) × 100 % Fig. 3. Temperature-dependent dynamic light scattering results of DMP aggregates at different temperatures.
2.6. Release behavior of microcapsules The release behavior of MCs prepared with different temperatures was determined by adapting a previously reported method [23]. Briefly, dried MC particles (0.1 g) were accurately weighed and transferred to a 250 mL three-neck round-bottomed flask equipped with a stirrer at room temperature. A mixture of hexane-ethyl alcohol (17: 2, v/v) were used as the release media (100 mL). A 0.2 mL of the mixed solvents was withdrawn at predetermined intervals and simultaneously added into the same volume of release media. The concentration of pendimethalin was analyzed by the HPLC system described above. The cumulative release proportion was calculated using the following equation:
2.4. Characterization of microcapsules The surface morphologies of obtained MCs and capsule shells were observed using scanning electron microscopy (SEM; S4800; Hitachi, Tokyo, Japan). The pore size on MC surface were counted from SEM images. The dynamic encapsulation process of MCs was observed using optical microscopy (Olympus CX41-32RFL; Tokyo, Japan). The particle sizes of DMP solution (0.2 %, w/w, dissolved in deionized water) and MCs were measured by temperature-dependent dynamic light scattering (DLS, Malvern Zetasizer Nano ZS, Malvern Instruments Ltd, UK) at an angle of 173°. The mechanical property of the single MC was determined using an atomic force microscopy (AFM) with a ScanAsyst-air probe (Bruker, Germany) at 25 °C.
Cumulative release proportion (%) = (mass of pendimethalin in the release medium at time t/ mass of pendimethalin in the dried MC particles) × 100 %
2.5. Determination of encapsulation efficiency and drug loading content of microcapsules
3. Results and discussion
The encapsulation efficiency and drug loading capacity of EPN-MCs were measured by high-performance liquid chromatography (HPLC) system (Agilent 1200; Agilent Technologies; Santa Clara, CA) equipped with an ultraviolet detector [37]. A given amount of dried MC particles
3.1. Preparation and characterization of microcapsules at the Tscp of DMP In this study, DMP, a reversibly temperature-responsive polyamine material with the Tscp of 61 ± 3 °C, was chosen as crosslinker. Previous 3
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Fig. 4. Encapsulation process of MCs prepared at different reaction temperatures. Scale bars are 20 μm.
Fig. 5. Schematic illustration of the major steps involved in the synthesis of porous MCs.
results demonstrated that the MCs prepared at 70 °C (above Tscp) exhibited porous surface morphology, while those fabricated at 50 °C (below Tscp) showed imporous surface [34]. Nevertheless, no experimental data were available for the reaction temperature around the Tscp as well as for a wider temperature range, which limited the insights of the temperature effect and the pore forming mechanism of MCs. In order to get an in-depth understanding, we chose 60 °C (close to its Tscp) as the reaction temperature to fabricate MCs. As shown in Fig. 1, the surface porous MCs were successfully obtained with pore size of ca.
150 nm (Fig. 2F). These results are supplementary to the previous research, suggesting that such porous MCs can also be prepared at other temperature, and thus the operating parameters of porous MCs have been broadened. 3.2. Preparation and characterization of microcapsules fabricated at wide temperature range The above results displayed that porous MCs could be synthesized at 4
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to measure the diameter change of DMP solution at six temperatures (Fig. 3). As the temperature increased, the size of DMP aggregates grows up from nanometer to submicrometer. The sizes of DMP aggregates were ca. 40 nm below the Tscp of DMP, and they increased sharply with the temperature heated to 60 °C. The sizes reached a plateau at the temperatures higher than 70 °C, indicating that the DMP was nearly insoluble at high temperature. These results suggested that the diameter of DMP aggregates is positive correlation with the reaction temperature, and high temperature resulted in the reduction of DMP solubility. 3.3. The dynamic morphological evolution during the encapsulation process at different reaction temperatures and the encapsulation mechanism In this study, we found that the surface morphology of MCs was strongly affected by reaction temperature. In addition, the pore density on MC surface showed a decreasing tendency or even disappeared when reaction temperature was over 70 °C, which was not as predicted. Therefore, the encapsulation process of MCs at different reaction times and temperatures were caught, aiming to reveal such eccentric phenomenon and illustrate the correlation between reaction temperature and MC morphology (Fig. 4). When DMP solutions were added into the O/W emulsion, the interfacial polymerization took place immediately. There were no nucleation points after 60 min at temperature of 60 °C (Fig. 4A), while spherical morphology began to appear only after 35 min at the temperature above 70 °C (Fig. 4B). When at 60 °C, the poorly developed shell wall formed after 80 min, but MCs were easily deformed or fractured after water evaporated resulting from the poor strength of shell. Higher temperature could reduce packing time, which was confirmed from the emergence times of intact MCs, approximately 50 min at 70 °C, 35 min at 80 °C and 15 min at 90 °C (Fig. 4B–D). In addition, once the spherical MCs formed at high temperatures (80 °C and 90 °C), no large and obvious change were observed for both the surface and size of MCs, which was in agreement with the SEM results (Fig. 2D and E). The morphology evolution of encapsulation process revealed that high temperature leaded to fast encapsulating. As the aforementioned mechanism, DMP aggregates deposited and were locked on the loose capsule shells via a gentle shell-forming procedure to generate pores. Both the size and volume of DMP aggregates elevated with increasing temperatures, leading to more aggregates deposited on the capsule shells, and further resulting in larger pore size and higher pore density. Nevertheless, the higher temperature accelerated the interfacial polymerization reaction of shell formation, so that inadequate time was left for the deposition of DMP aggregates owing to the quicker encapsulation. And thus, the pore size and pore density decreased at temperature above 80 °C. Based on the above discussion, a conclusion can be drawn that the porous MCs with tunable porous morphology can be easily fabricated by adjusting the operation temperature, which affected the size and volume of DMP aggregates as well as the encapsulation time. Based on the encapsulation evolution shown in Fig. 4 and 5 illustrated schematic diagram of the formation mechanism of porous MCs. Firstly, the stable O/W emulsion was prepared at room temperature. The loose capsule shell formed progressively at the oil-water interface layer as the DMP solution added dropwise at certain temperature. When temperature maintained closed to Tscp of DMP, the DMP aggregates deposited randomly on the loose shell layer because of the weak repulsive force between the aggregates and capsule shells with increasing temperature. The cured capsule shell generated spending approximately 80 min (Fig. 4), and during this stage, the compactness and crosslinking degree of capsule shells became higher, the DMP aggregates were immobilized on the cured shells, where several aggregates embed into shells with certain depth and some deposited on the outer surface of capsules. After the encapsulation process is terminated, the system was cooled to room temperature, DMP aggregates were redissolved in water and leaved small pores on the surface to form
Fig. 6. (A) Mean diameter, (B) encapsulation efficiency and drug loading content of MCs prepared with different temperatures.
the Tscp of DMP (60 °C). But it can also be seen that the pore diameter at 60 °C was significantly smaller than previously reported at 70 °C (ca. 400 nm) [34]. Therefore, the reaction temperature plays a vital role on the pore size of MCs, and an in-deep investigation on operating temperature can not only help to prepare the MCs with tunable morphological, but also offer an insight on the pore-forming mechanism. We thus designed a series of temperatures (from 40 °C to 90 °C) to fabricate MCs while all other parameters were constant, which enabled us to focus on the temperature effect on the encapsulation procedure. The representative SEM images of obtained MCs were shown in Fig. 2. The surface morphologies of as-prepared MCs were imporous when the reaction temperatures were maintained at 40 °C and 50 °C, respectively (Fig. 2A and B). The MCs exhibited rough surface and adhered to each other at 40 °C while they became smooth at 50 °C, indicating that the MC shells were softer at lower temperature. Both the pore size (from ca. 21 nm–237 nm, Fig. 2F) and pore density on MC surface increased with elevating temperature from 50 °C (Fig. 2B) to 70 °C (Fig. 2C). Surprisingly, the pore sizes were declined along with further increasing temperature (Fig. 2D), especially when the temperature was heated to 90 °C, there were no pores on MC surface (Fig. 2E). The solubility of DMP decreased with increasing temperature, DMP molecules precipitated from water and formed into aggregates at temperature above its Tscp. When the reaction temperature was high than the Tscp of DMP, DMP aggregates deposited and were locked on the loose MC wall layer via a mild shell-forming procedure. After the system was cooled to room temperature, DMP aggregates were redissolved in water to generate pores [34]. As a result, the size of DMP aggregates depends on the temperature, which further affects the porous morphology on capsule surface. DLS experiment was carried out 5
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Fig. 7. (A) SEM images and (B) mechanical strengths of MC shells prepared with different temperatures: (1) 40 °C, (2) 50 °C, (3) 60 °C, (4) 70 °C, (5) 80 °C and (6) 90 °C, (C) mean thickness and Young's modulus of MC shells prepared with different temperatures.
porous MCs. As for temperature below the Tscp of DMP, DMP was soluble in water with no aggregates, so that the as-prepared MCs exhibited smooth surface without any pores. Moreover, the formation of cured capsule shells only took less than 30 min at temperature above Tscp of DMP, such short encapsulation time was inadequate for the deposition and immobilization of DMP aggregates, which resulted in imporous surface of MCs. 3.4. Particle size, encapsulation efficiency and drug loading content of microcapsules prepared at different temperatures The diameters of MCs increased slightly (from 11.6 μm to 16.3 μm) with increasing temperatures (Fig. 6A), which may be due to the instable emulsion tending to aggregate at high temperature [38]. The MCs also displayed wide size distribution resulting from turbulent flow around the propeller [39]. The effect of temperature on the encapsulation efficiency and drug loading content of MCs were investigated, as shown in Fig. 6B. The encapsulation efficiencies of all MC samples were above 91 %, and they increased lightly at higher reaction temperature, suggesting that large part of payload was successfully encapsulated in the intracapsular cavity. In addition, the loading contents were 49–52 % with no apparent connection to temperatures.
Fig. 8. Release behavior of MCs prepared with different temperatures.
Among them, the shell samples below 60 °C exhibited strongly corrugated shrinking shapes (Fig. 7A1–A3), and those prepared at 70 and 80 °C displayed porous surface morphologies (Fig. 7A4 and A5), which was accordant with the morphologies of as-prepared MCs (Fig. 2A–D). The shell systems developed progressively more rigid and undeformed as temperature further raised (Fig. 7A5 and A6), which may be related to heat-induced rigidity. Similar results were obtained by Zheng et al. [40]. It can also be seen that pores on capsule shells were declined with increasing temperature from 70 °C to 90 °C, which was also in accordance with our aforementioned results (Fig. 2). The fold of shells is
3.5. Morphology, thickness and mechanical property of microcapsule shells at different temperatures The morphologies of capsule shells were obtained by removing the payload and observed using SEM (Fig. 7A). All capsule shells were smooth and irregular shapes owing to the removal of loaded cargo. 6
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formed by stacking two layers [41]. Based on this, the thickness of the capsule shell was counted, and they were enhanced from 86 nm to 257 nm as temperature increased (Fig. 7C). The above results indicated that the reaction temperatures affect the thickness of shells, and high temperature leads to thicker shells. The mechanical strengths of MCs were determined using atomic force microscopy (Fig. 7B), and the values of Young's modulus were summarized (Fig. 7C). The Young's modulus represents the material stiffness and is often utilized to describe the elastic deformation [42]. The Young's modulus of MCs prepared at 40 °C and 50 °C were less than 30 MPa, and this index was strongly associated with reaction temperature. As the temperature increased from 60 °C to 90 °C, the values enhanced sharply from 42 to 81 MPa, suggesting enhanced mechanical strength. The above results suggested that the morphologies, thickness and mechanical properties of MCs were closely linked to the reaction temperature. The accelerated interfacial polymerization reaction at high temperature leaded to thicker and stronger shell systems, and further maintained their indeformable shapes.
CRediT authorship contribution statement Xianpeng Zhang: Investigation, Methodology, Formal analysis, Writing - original draft. Luxia Zhang: Formal analysis, Validation, Writing - original draft. Daxia Zhang: Formal analysis, Validation. Sisi Liu: Formal analysis, Validation. Dengguo Wei: Supervision, Writing review & editing, Funding acquisition. Feng Liu: Conceptualization, Supervision, Project administration, Writing - review & editing. Declaration of Competing Interest The authors declare no competing financial interest. Acknowledgement This work was supported by Huazhong Agricultural University Scientific & Technological Self-innovation Foundation (No. 2015RC013). References
3.6. Release behavior of microcapsules prepared at different temperatures
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In the present work, the hexane-ethyl alcohol mixture was employed as a medium to simulate the release profile of MC samples on account of their large dissolving capacity and shortening the trial period [41]. The release rate of MCs prepared at 70 °C was the fastest, it reached 85 % in the first six hours (Fig. 8). The cumulative release of MCs prepared at 40, 50 and 70 °C were 53 %, 48 % and 65 % in the first six hours, respectively, while the remaining two merely reached 20 % (80 °C) and 9% (90 °C). The transfer of the core material from MC cavity into the outer environment is critical for the controllable release profiles, which can be adjusted by the microstructure of capsule shells and the particle size of MCs [43]. In this study, three main factors, including pore size, shell thickness and MC size, may contribute to the tunable release behavior of MCs [25,44]. The release rate increased with increasing pore size (the release of MCs at 70 °C＞60 °C＞others). As for the MCs with no pores, the shell thickness may play an important role on the release behavior, in which the thicker shells leaded to slower release rate (the release of MCs at 40 °C＞50 °C＞90 °C). The precise and controlled release of MCs is essential in practical applications, and thus, the release mechanism of such MCs remains to be further investigated. 4. Conclusions In this study, polymeric MCs with tailorable surface morphologies were prepared using DMP as crosslinker by changing the reaction temperature. The pore size on capsule surface was easily tuned from nonporous to ca. 237 nm in diameter with temperature up to 70 °C, whereas they decreased with further increasing temperature up to 90 °C. The dynamic evolution of encapsulation process illuminated that DMP molecular gathered into aggregates and deposited on capsule shells via a mild polymerization reaction at temperature close its Tscp, which leaded to porous morphology on MC surface after the system was cooled. The polymerization reaction of shell-forming was so fast that was adverse for the deposition of DMP aggregates on the loose capsule shells at temperature higher than 70 °C, resulting in the decreasing tendency of pore size on capsule shells. Moreover, operating temperature affected the thickness and mechanical strength of MCs, in which higher temperature enabled to generate thicker thickness and larger mechanical strength owing to improved reactivity at high temperature. In addition, the release behavior of MCs was controlled by adjusting the pore size and shell structure. This work provided an insight about temperature effect to prepare tunable MCs, which has a promising application to encapsulate lipophilic functional compounds for controlled release. 7
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X. Zhang, et al. [21] M.H. Lee, K.C. Hribar, T. Brugarolas, N.P. Kamat, J.A. Burdick, D. Lee, Harnessing interfacial phenomena to program the release properties of hollow microcapsules, Adv. Funct. Mater. 22 (1) (2012) 131–138. [22] X.L. Yang, X.J. Ju, X.T. Mu, W. Wang, R. Xie, Z. Liu, L.Y. Chu, Core-shell chitosan microcapsules for programmed sequential drug release, ACS Appl. Mater. Int. 8 (16) (2016) 10524–10534. [23] B. Liu, Y. Wang, F. Yang, H. Cui, D. Wu, Development of a chlorantraniliprole microcapsule formulation with a high loading content and controlled-release property, J. Agric. Food Chem. 66 (26) (2018) 6561–6568. [24] N.A. Wagdare, A.T. Marcelis, R.M. Boom, C.J. van Rijn, Porous microcapsule formation with microsieve emulsification, J. Colloid Interface Sci. 355 (2) (2011) 453–457. [25] K. Liang, G.K. Such, Z. Zhu, S.J. Dodds, A.P. Johnston, J. Cui, H. Ejima, F. Caruso, Engineering cellular degradation of multilayered capsules through controlled crosslinking, ACS Nano 6 (11) (2012) 10186–10194. [26] Y. Yang, Z. Wei, C. Wang, Z. Tong, Versatile fabrication of nanocomposite microcapsules with controlled shell thickness and low permeability, ACS Appl. Mater. Int. 5 (7) (2013) 2495–2502. [27] M. Ina, A.P. Zhushma, N.V. Lebedeva, M. Vatankhah-Varnoosfaderani, S.D. Olson, S.S. Sheiko, The design of wrinkled microcapsules for enhancement of release rate, J. Colloid Interface Sci. 478 (2016) 296–302. [28] S. Cao, R. Tang, G. Sudlow, Z. Wang, K.K. Liu, J. Luan, S. Tadepalli, A. Seth, S. Achilefu, S. Singamaneni, Shape-dependent biodistribution of biocompatible silk microcapsules, ACS Appl. Mater. Int. 11 (5) (2019) 5499–5508. [29] S. Nikolov, A. Fernandez-Nieves, A. Alexeev, Phagocyte-inspired smart microcapsules, ACS Macro Lett. 8 (4) (2019) 421–426. [30] B. Jiang, X. Wang, D. Wu, Fabrication of microencapsulated phase change materials with TiO2/Fe3O4 hybrid shell as thermoregulatory enzyme carriers: a novel design of applied energy microsystem for bioapplications, Appl. Energy 201 (2017) 20–33. [31] L.S. Kuck, J.L. Wesolowski, C.P.Z. Norena, Effect of temperature and relative humidity on stability following simulated gastro-intestinal digestion of microcapsules of Bordo grape skin phenolic extract produced with different carrier agents, Food Chem. 230 (2017) 257–264. [32] Y.-L. Du, G.-Q. Huang, H.-O. Wang, J.-X. Xiao, Effect of high coacervation temperature on the physicochemical properties of resultant microcapsules through induction of Maillard reaction between soybean protein isolate and chitosan, J. Food Eng. 234 (2018) 91–97. [33] D. Fu, Y. Su, B. Xie, G. Liu, Z. Li, K. Jiang, D. Wang, Pore decoration on
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Colloids and Surfaces A journal homepage: www.elsevier.com/locate/colsurfa
Mechanism of the temperature-responsive material regulating porous morphology on epoxy phenolic novolac resin microcapsule surface
T
Xianpeng Zhanga, Luxia Zhangb, Daxia Zhangc, Sisi Liub,*, Dengguo Weib,*, Feng Liuc,* a
College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, PR China College of Science, Huazhong Agricultural University, Wuhan, Hubei, 430070, PR China c Key Laboratory of Pesticide Toxicology & Application Technique, Shandong Agricultural University, Tai’an, Shandong, 271018, PR China b
GRAPHICAL ABSTRACT
ARTICLE INFO
ABSTRACT
Keywords: Surface porous microcapsules Tunable pore size Temperature effect Pore formation mechanism
Porous microcapsules (MCs) with tailorable surface morphology are indispensable in practical applications because of their large surface area and controlled release. In this study, epoxy phenolic novolac resin MCs were prepared with temperature-responsive 2,4,6-tris(dimethylaminomethyl)phenol (DMP) as crosslinker. Reaction temperature was proved to generate distinct effects on MC porous morphology, shell thickness, mechanical strength and release behavior. The MC surface varied from nonporous to dense small pores (ca. 237 nm in diameter) with increasing temperature from 40 °C to 70 °C, but they showed decreasing tendency at higher temperature (＞70 °C). The encapsulation process illuminated that DMP aggregates formed and deposited on the loose shells at 60 °C and 70 °C (close to the so-called cloud point (Tscp) of DMP), leading to porous morphology. Nevertheless, at temperature far below or above the Tscp of DMP (＜50 °C or ＞70 °C), DMP kept its solubility in water or insufficiently deposited on the shells, which resulted in no pores existed. Higher temperature promoted the reactivity to generate thicker shells and larger mechanical strength, further leading to prolong payload release. The present work provided an insight about the reaction temperature to prepare tunable MCs, which can be employed to encapsulate lipophilic components in agriculture field.
1. Introduction Microcapsules (MCs) containing various active substances pose
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immense advantages in a wide range of applications, including drug delivery, self-healing materials, environmental engineering and industrial applications [1–6]. One of the most prominent characteristics
Corresponding authors. E-mail addresses: [email protected] (S. Liu), [email protected] (D. Wei), [email protected] (F. Liu).
https://doi.org/10.1016/j.colsurfa.2020.124581 Received 9 January 2020; Received in revised form 6 February 2020; Accepted 10 February 2020 Available online 11 February 2020 0927-7757/ © 2020 Elsevier B.V. All rights reserved.
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of MCs is their controlled release, which can be easily tailored by varying the microstructure of the capsule shells [7–9]. Porous MCs are known to have large specific surface area and confined inner space, and have been extended to fit different applications as needed [10–12]. Nowadays, porous MCs with tunable pore size and pore density have become a research hotspot because of their versatility and universality [13,14]. Along with the development of microencapsulation technique in recent years, MCs with precisely tailoring structures in the micrometer/ nanometer region are highly promising owing to the possibility to achieve core delivery on demand [15,16]. The key element for the preparation of smart payload carriers depends on the shell structures [17]. Some researcher commitment to modify the capsule shells via a chemical or physical change that can be triggered by external stimulus, such as pH, temperature, ultrasound, or light [18–21]; based on such mechanism, the cargo release from MCs is either in an “ON” state or in an “OFF” state, this also results in complex architecture and synthesis of MCs [22]. Others focused on physical response release that induced physical changes to the capsule structures, such as surface morphology, mechanical strength, thickness, pore size, etc [23–27]. Comparably, it is easier to fabricate MCs with tunable profile by varying suitable fabrication parameters. In addition, the synthesis of MCs is a complex procedure due to the complicated compositions and diversiform reaction conditions. The differences in operating parameters largely determine the physicochemical properties of as-prepared MCs, which are essential for their practical applications [28,29]. Among these operating parameters, reparation temperature can exert a vital influence on capsule properties, since it affects the material solubility, phase change behavior and reactivity, etc [30–33]. Therefore, it is required that the operating conditions should be precisely governed to guarantee the controllable structure and profile of MCs. Recently, we successfully prepared porous MCs with tunable pore size by regulating the amount of crosslinker, ratio of core material to shell or epoxy value of wallforming material [13,34]. Additionally, the influence of operating temperature was important for the synthesis of such porous MCs, in which changing reaction temperature could markedly affect the phase change behavior and solubility of the crosslinker, and further determined the final morphology of MCs. Detailed investigation on temperature effect will not only give theoretical understand, but may also offer the route to accurately prepare porous MCs. Therefore, the mechanism needs to be further confirmed with a wider range of reaction temperature. Moreover, the physicochemical properties and poreforming mechanism of such MCs based on reaction temperature have not been thoroughly studied. Pendimethalin (N-(l-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzenamine) is a dinitroaniline herbicide used for the control annual grasses and broadleaf weeds. However, pendimethalin has high toxicity to aquatic organisms; the emulsifiable concentrate is most widely used formulation due to its inferior water solubility (0.3 mg/L at 20 °C), all of which lead to toxicity risks and environmental pollution [35,36]. The controlled release technology has been highly desirable and emerged as an alternative approach. We thus chose pendimethalin as a model payload to solve the possible negative effects and improve its utilization. In the present study, epoxy phenolic novolac resin-based MCs (EPNMCs) were fabricated using 2,4,6-tris(dimethylaminomethyl)phenol (DMP, a temperature-responsive material with the so-called cloud point (Tscp) of 61 ± 3 °C) as crosslinker at temperatures both above and below its Tscp. The effects of temperature on the surface morphology, pore size, and particle size as well as thickness, mechanical strength and release behavior were systematically investigated. This work provided an insight on the reaction temperature to prepare porous MCs with tunable surface morphology, which has potential applications in lipophilic functional component encapsulation for controlled release in agriculture field.
Fig. 1. SEM image of porous MCs prepared using DMP as crosslinker at 60 °C. The inset is the high-magnification image.
2. Materials and methods 2.1. Materials Epoxy phenolic novolac resin (EPN), with epoxy value of 0.46 mol per 100 g, was purchased from Shanghai Resin Plant, China. 2,4,6-tris (dimethylaminomethyl)phenol (DMP), used as a crosslinker, was purchased from Sigma-Aldrich Chemical Co. (Shanghai, China). Pendimethalin (purity 99 %), used as a model core, was purchased from Sigma-Aldrich Chemical Co. (Shanghai, China). Polyoxyethylene sorbitan monooleate (Tween-80) was used as surfactant. All other reagents were of analytical grade and used without further purification. Deionized water was used in all experiments. 2.2. Preparation of microcapsules EPN-MCs were prepared by an interfacial emulsion polymerization technique according to previously reported methods [13]. Briefly, the oil phase consisted of pendimethalin and wall-forming material was obtained by dissolving pendimethalin (12 g) and EPN (3 g) in xylene (4 mL). The aqueous phase consisted of surfactant was obtained by dissolving Tween-80 (1.2 g) in deionized water (75 mL). The oil phase was dispersed in aqueous phase and homogenized at 10,000 rpm for 120 s with a homogenizer (IKA T18, Digital ULTRA-TURRAX, Germany) to generate a stable oil-in-water (O/W) emulsion. Subsequently, the homogeneous emulsion was poured into a three-necked round-bottom flask equipped with a water thermostat bath and mechanical stirrer. The system was heated to certain temperature (ranging from 40 °C to 90 °C), and then, DMP solution (0.18 g of DMP dissolved in 3.5 mL deionized water) was added dropwise to the system under constant stirring at 300 rpm. The polymerization reaction proceeded for 5 h to obtain core-shell-structured MCs. At last, the reaction system was cooled down to room temperature, the microcapsules were washed with deionized water and then dried in a vacuum oven at 40 °C for 72 h. 2.3. Preparation of microcapsule shells The microcapsule shells were obtained by removing the payload core. Briefly, a given amount of pendimethalin-loaded MCs was dissolved in 5 mL of methanol, and then the solution was ultrasonicated for 2 h to break the capsule shells. Subsequently, the mixture was centrifuged at 10,000 rpm and the supernatant was discarded. The precipitate was washed with methanol and deionized water successively, and then, dried in a vacuum oven at 40 °C for 4 h. 2
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Fig. 2. SEM images of MCs prepared by changing the reaction temperatures: (A) 40 °C, (B) 50 °C, (C) 70 °C, (D) 80 °C and (E) 90 °C, and (F) pore diameter of MCs prepared at different reaction temperatures.
(0.5 g was dissolved in hexane 50 mL, and then the system was disrupted with ultrasound for 2 h to ensure the complete burst of the MC samples. The mixture was centrifuged at 10,000 rpm and the supernatant was collected. The pendimethalin concentration in the supernatant was measured by UV detector at a wavelength of 238 nm. The mobile phase of the HPLC system was composed of methanol and water (90:10, v/v) at a flow rate of 1 mL/min. The column temperature was room temperature. The encapsulation efficiency and drug loading content were calculated using the following Equation: Encapsulation efficiency = (mass of pendimethalin in MC particles/ total mass of pendimethalin used for the MC particles preparation) × 100 % Drug loading content = (mass of pendimethalin in MC particles/total mass of MC particles) × 100 % Fig. 3. Temperature-dependent dynamic light scattering results of DMP aggregates at different temperatures.
2.6. Release behavior of microcapsules The release behavior of MCs prepared with different temperatures was determined by adapting a previously reported method [23]. Briefly, dried MC particles (0.1 g) were accurately weighed and transferred to a 250 mL three-neck round-bottomed flask equipped with a stirrer at room temperature. A mixture of hexane-ethyl alcohol (17: 2, v/v) were used as the release media (100 mL). A 0.2 mL of the mixed solvents was withdrawn at predetermined intervals and simultaneously added into the same volume of release media. The concentration of pendimethalin was analyzed by the HPLC system described above. The cumulative release proportion was calculated using the following equation:
2.4. Characterization of microcapsules The surface morphologies of obtained MCs and capsule shells were observed using scanning electron microscopy (SEM; S4800; Hitachi, Tokyo, Japan). The pore size on MC surface were counted from SEM images. The dynamic encapsulation process of MCs was observed using optical microscopy (Olympus CX41-32RFL; Tokyo, Japan). The particle sizes of DMP solution (0.2 %, w/w, dissolved in deionized water) and MCs were measured by temperature-dependent dynamic light scattering (DLS, Malvern Zetasizer Nano ZS, Malvern Instruments Ltd, UK) at an angle of 173°. The mechanical property of the single MC was determined using an atomic force microscopy (AFM) with a ScanAsyst-air probe (Bruker, Germany) at 25 °C.
Cumulative release proportion (%) = (mass of pendimethalin in the release medium at time t/ mass of pendimethalin in the dried MC particles) × 100 %
2.5. Determination of encapsulation efficiency and drug loading content of microcapsules
3. Results and discussion
The encapsulation efficiency and drug loading capacity of EPN-MCs were measured by high-performance liquid chromatography (HPLC) system (Agilent 1200; Agilent Technologies; Santa Clara, CA) equipped with an ultraviolet detector [37]. A given amount of dried MC particles
3.1. Preparation and characterization of microcapsules at the Tscp of DMP In this study, DMP, a reversibly temperature-responsive polyamine material with the Tscp of 61 ± 3 °C, was chosen as crosslinker. Previous 3
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Fig. 4. Encapsulation process of MCs prepared at different reaction temperatures. Scale bars are 20 μm.
Fig. 5. Schematic illustration of the major steps involved in the synthesis of porous MCs.
results demonstrated that the MCs prepared at 70 °C (above Tscp) exhibited porous surface morphology, while those fabricated at 50 °C (below Tscp) showed imporous surface [34]. Nevertheless, no experimental data were available for the reaction temperature around the Tscp as well as for a wider temperature range, which limited the insights of the temperature effect and the pore forming mechanism of MCs. In order to get an in-depth understanding, we chose 60 °C (close to its Tscp) as the reaction temperature to fabricate MCs. As shown in Fig. 1, the surface porous MCs were successfully obtained with pore size of ca.
150 nm (Fig. 2F). These results are supplementary to the previous research, suggesting that such porous MCs can also be prepared at other temperature, and thus the operating parameters of porous MCs have been broadened. 3.2. Preparation and characterization of microcapsules fabricated at wide temperature range The above results displayed that porous MCs could be synthesized at 4
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to measure the diameter change of DMP solution at six temperatures (Fig. 3). As the temperature increased, the size of DMP aggregates grows up from nanometer to submicrometer. The sizes of DMP aggregates were ca. 40 nm below the Tscp of DMP, and they increased sharply with the temperature heated to 60 °C. The sizes reached a plateau at the temperatures higher than 70 °C, indicating that the DMP was nearly insoluble at high temperature. These results suggested that the diameter of DMP aggregates is positive correlation with the reaction temperature, and high temperature resulted in the reduction of DMP solubility. 3.3. The dynamic morphological evolution during the encapsulation process at different reaction temperatures and the encapsulation mechanism In this study, we found that the surface morphology of MCs was strongly affected by reaction temperature. In addition, the pore density on MC surface showed a decreasing tendency or even disappeared when reaction temperature was over 70 °C, which was not as predicted. Therefore, the encapsulation process of MCs at different reaction times and temperatures were caught, aiming to reveal such eccentric phenomenon and illustrate the correlation between reaction temperature and MC morphology (Fig. 4). When DMP solutions were added into the O/W emulsion, the interfacial polymerization took place immediately. There were no nucleation points after 60 min at temperature of 60 °C (Fig. 4A), while spherical morphology began to appear only after 35 min at the temperature above 70 °C (Fig. 4B). When at 60 °C, the poorly developed shell wall formed after 80 min, but MCs were easily deformed or fractured after water evaporated resulting from the poor strength of shell. Higher temperature could reduce packing time, which was confirmed from the emergence times of intact MCs, approximately 50 min at 70 °C, 35 min at 80 °C and 15 min at 90 °C (Fig. 4B–D). In addition, once the spherical MCs formed at high temperatures (80 °C and 90 °C), no large and obvious change were observed for both the surface and size of MCs, which was in agreement with the SEM results (Fig. 2D and E). The morphology evolution of encapsulation process revealed that high temperature leaded to fast encapsulating. As the aforementioned mechanism, DMP aggregates deposited and were locked on the loose capsule shells via a gentle shell-forming procedure to generate pores. Both the size and volume of DMP aggregates elevated with increasing temperatures, leading to more aggregates deposited on the capsule shells, and further resulting in larger pore size and higher pore density. Nevertheless, the higher temperature accelerated the interfacial polymerization reaction of shell formation, so that inadequate time was left for the deposition of DMP aggregates owing to the quicker encapsulation. And thus, the pore size and pore density decreased at temperature above 80 °C. Based on the above discussion, a conclusion can be drawn that the porous MCs with tunable porous morphology can be easily fabricated by adjusting the operation temperature, which affected the size and volume of DMP aggregates as well as the encapsulation time. Based on the encapsulation evolution shown in Fig. 4 and 5 illustrated schematic diagram of the formation mechanism of porous MCs. Firstly, the stable O/W emulsion was prepared at room temperature. The loose capsule shell formed progressively at the oil-water interface layer as the DMP solution added dropwise at certain temperature. When temperature maintained closed to Tscp of DMP, the DMP aggregates deposited randomly on the loose shell layer because of the weak repulsive force between the aggregates and capsule shells with increasing temperature. The cured capsule shell generated spending approximately 80 min (Fig. 4), and during this stage, the compactness and crosslinking degree of capsule shells became higher, the DMP aggregates were immobilized on the cured shells, where several aggregates embed into shells with certain depth and some deposited on the outer surface of capsules. After the encapsulation process is terminated, the system was cooled to room temperature, DMP aggregates were redissolved in water and leaved small pores on the surface to form
Fig. 6. (A) Mean diameter, (B) encapsulation efficiency and drug loading content of MCs prepared with different temperatures.
the Tscp of DMP (60 °C). But it can also be seen that the pore diameter at 60 °C was significantly smaller than previously reported at 70 °C (ca. 400 nm) [34]. Therefore, the reaction temperature plays a vital role on the pore size of MCs, and an in-deep investigation on operating temperature can not only help to prepare the MCs with tunable morphological, but also offer an insight on the pore-forming mechanism. We thus designed a series of temperatures (from 40 °C to 90 °C) to fabricate MCs while all other parameters were constant, which enabled us to focus on the temperature effect on the encapsulation procedure. The representative SEM images of obtained MCs were shown in Fig. 2. The surface morphologies of as-prepared MCs were imporous when the reaction temperatures were maintained at 40 °C and 50 °C, respectively (Fig. 2A and B). The MCs exhibited rough surface and adhered to each other at 40 °C while they became smooth at 50 °C, indicating that the MC shells were softer at lower temperature. Both the pore size (from ca. 21 nm–237 nm, Fig. 2F) and pore density on MC surface increased with elevating temperature from 50 °C (Fig. 2B) to 70 °C (Fig. 2C). Surprisingly, the pore sizes were declined along with further increasing temperature (Fig. 2D), especially when the temperature was heated to 90 °C, there were no pores on MC surface (Fig. 2E). The solubility of DMP decreased with increasing temperature, DMP molecules precipitated from water and formed into aggregates at temperature above its Tscp. When the reaction temperature was high than the Tscp of DMP, DMP aggregates deposited and were locked on the loose MC wall layer via a mild shell-forming procedure. After the system was cooled to room temperature, DMP aggregates were redissolved in water to generate pores [34]. As a result, the size of DMP aggregates depends on the temperature, which further affects the porous morphology on capsule surface. DLS experiment was carried out 5
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Fig. 7. (A) SEM images and (B) mechanical strengths of MC shells prepared with different temperatures: (1) 40 °C, (2) 50 °C, (3) 60 °C, (4) 70 °C, (5) 80 °C and (6) 90 °C, (C) mean thickness and Young's modulus of MC shells prepared with different temperatures.
porous MCs. As for temperature below the Tscp of DMP, DMP was soluble in water with no aggregates, so that the as-prepared MCs exhibited smooth surface without any pores. Moreover, the formation of cured capsule shells only took less than 30 min at temperature above Tscp of DMP, such short encapsulation time was inadequate for the deposition and immobilization of DMP aggregates, which resulted in imporous surface of MCs. 3.4. Particle size, encapsulation efficiency and drug loading content of microcapsules prepared at different temperatures The diameters of MCs increased slightly (from 11.6 μm to 16.3 μm) with increasing temperatures (Fig. 6A), which may be due to the instable emulsion tending to aggregate at high temperature [38]. The MCs also displayed wide size distribution resulting from turbulent flow around the propeller [39]. The effect of temperature on the encapsulation efficiency and drug loading content of MCs were investigated, as shown in Fig. 6B. The encapsulation efficiencies of all MC samples were above 91 %, and they increased lightly at higher reaction temperature, suggesting that large part of payload was successfully encapsulated in the intracapsular cavity. In addition, the loading contents were 49–52 % with no apparent connection to temperatures.
Fig. 8. Release behavior of MCs prepared with different temperatures.
Among them, the shell samples below 60 °C exhibited strongly corrugated shrinking shapes (Fig. 7A1–A3), and those prepared at 70 and 80 °C displayed porous surface morphologies (Fig. 7A4 and A5), which was accordant with the morphologies of as-prepared MCs (Fig. 2A–D). The shell systems developed progressively more rigid and undeformed as temperature further raised (Fig. 7A5 and A6), which may be related to heat-induced rigidity. Similar results were obtained by Zheng et al. [40]. It can also be seen that pores on capsule shells were declined with increasing temperature from 70 °C to 90 °C, which was also in accordance with our aforementioned results (Fig. 2). The fold of shells is
3.5. Morphology, thickness and mechanical property of microcapsule shells at different temperatures The morphologies of capsule shells were obtained by removing the payload and observed using SEM (Fig. 7A). All capsule shells were smooth and irregular shapes owing to the removal of loaded cargo. 6
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formed by stacking two layers [41]. Based on this, the thickness of the capsule shell was counted, and they were enhanced from 86 nm to 257 nm as temperature increased (Fig. 7C). The above results indicated that the reaction temperatures affect the thickness of shells, and high temperature leads to thicker shells. The mechanical strengths of MCs were determined using atomic force microscopy (Fig. 7B), and the values of Young's modulus were summarized (Fig. 7C). The Young's modulus represents the material stiffness and is often utilized to describe the elastic deformation [42]. The Young's modulus of MCs prepared at 40 °C and 50 °C were less than 30 MPa, and this index was strongly associated with reaction temperature. As the temperature increased from 60 °C to 90 °C, the values enhanced sharply from 42 to 81 MPa, suggesting enhanced mechanical strength. The above results suggested that the morphologies, thickness and mechanical properties of MCs were closely linked to the reaction temperature. The accelerated interfacial polymerization reaction at high temperature leaded to thicker and stronger shell systems, and further maintained their indeformable shapes.
CRediT authorship contribution statement Xianpeng Zhang: Investigation, Methodology, Formal analysis, Writing - original draft. Luxia Zhang: Formal analysis, Validation, Writing - original draft. Daxia Zhang: Formal analysis, Validation. Sisi Liu: Formal analysis, Validation. Dengguo Wei: Supervision, Writing review & editing, Funding acquisition. Feng Liu: Conceptualization, Supervision, Project administration, Writing - review & editing. Declaration of Competing Interest The authors declare no competing financial interest. Acknowledgement This work was supported by Huazhong Agricultural University Scientific & Technological Self-innovation Foundation (No. 2015RC013). References
3.6. Release behavior of microcapsules prepared at different temperatures
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In the present work, the hexane-ethyl alcohol mixture was employed as a medium to simulate the release profile of MC samples on account of their large dissolving capacity and shortening the trial period [41]. The release rate of MCs prepared at 70 °C was the fastest, it reached 85 % in the first six hours (Fig. 8). The cumulative release of MCs prepared at 40, 50 and 70 °C were 53 %, 48 % and 65 % in the first six hours, respectively, while the remaining two merely reached 20 % (80 °C) and 9% (90 °C). The transfer of the core material from MC cavity into the outer environment is critical for the controllable release profiles, which can be adjusted by the microstructure of capsule shells and the particle size of MCs [43]. In this study, three main factors, including pore size, shell thickness and MC size, may contribute to the tunable release behavior of MCs [25,44]. The release rate increased with increasing pore size (the release of MCs at 70 °C＞60 °C＞others). As for the MCs with no pores, the shell thickness may play an important role on the release behavior, in which the thicker shells leaded to slower release rate (the release of MCs at 40 °C＞50 °C＞90 °C). The precise and controlled release of MCs is essential in practical applications, and thus, the release mechanism of such MCs remains to be further investigated. 4. Conclusions In this study, polymeric MCs with tailorable surface morphologies were prepared using DMP as crosslinker by changing the reaction temperature. The pore size on capsule surface was easily tuned from nonporous to ca. 237 nm in diameter with temperature up to 70 °C, whereas they decreased with further increasing temperature up to 90 °C. The dynamic evolution of encapsulation process illuminated that DMP molecular gathered into aggregates and deposited on capsule shells via a mild polymerization reaction at temperature close its Tscp, which leaded to porous morphology on MC surface after the system was cooled. The polymerization reaction of shell-forming was so fast that was adverse for the deposition of DMP aggregates on the loose capsule shells at temperature higher than 70 °C, resulting in the decreasing tendency of pore size on capsule shells. Moreover, operating temperature affected the thickness and mechanical strength of MCs, in which higher temperature enabled to generate thicker thickness and larger mechanical strength owing to improved reactivity at high temperature. In addition, the release behavior of MCs was controlled by adjusting the pore size and shell structure. This work provided an insight about temperature effect to prepare tunable MCs, which has a promising application to encapsulate lipophilic functional compounds for controlled release. 7
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