Article pubs.acs.org/Langmuir
Controlled Fabrication of Multicompartmental Polymeric Microparticles by Sequential Micromolding via Surface-TensionInduced Droplet Formation Chang-Hyung Choi,†,§ Sung-Min Kang,†,§ Si Hyung Jin,† Hyunmin Yi,‡ and Chang-Soo Lee*,† †
Department of Chemical Engineering, Chungnam National University, Yuseong-gu, Daejeon, 305-764, Republic of Korea Department of Chemical and Biological Engineering, Tufts University, Medford, Massachusetts 02155, United States
‡
S Supporting Information *
ABSTRACT: Polymeric multicompartmental microparticles have significant potential in many applications due to the capability to hold various functions in discrete domains within a single particle. Despite recent progress in microfluidic techniques, simple and scalable fabrication methods for multicompartmental particles remain challenging. This study reports a simple sequential micromolding method to produce monodisperse multicompartmental particles with precisely controllable size, shape, and compartmentalization. Specifically, our fabrication procedure involves sequential formation of primary and secondary compartments in micromolds via surface-tensioninduced droplet formation coupled with simple photopolymerization. Results show that monodisperse bicompartmental particles with precisely controllable size, shape, and chemistry can be readily fabricated without sophisticated control or equipment. This technique is then extended to produce multicompartmental particles with controllable number of compartments and their size ratios through simple design of mold geometry. Also, core−shell particles with controlled number of cores for primary compartments can be readily produced by simple tuning of wettability. Finally, we demonstrate that the as-prepared multicompartmental particles can exhibit controlled release of multiple payloads based on design of particle compositions. Combined, these results illustrate a simple, robust, and scalable fabrication of highly monodisperse and complex multicompartmental particles in a controlled manner based on sequential micromolding.
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INTRODUCTION Multicompartmental polymeric particles have seen increasing use in a large number of applications, including imaging,1 catalyst support,2,3 drug delivery,4,5 biosensing,6 and directed self-assembly.7 These materials have the capability to impart discrete functionalities to each compartment within a single particle. As such, multicompartmental particles offer the ability to simultaneously deliver a multitude of payloads in a controlled manner, preferably upon the generation of various external stimuli.8−10 Furthermore, multicompartmental particles with different-sized compartments are well-suited for use as drug carriers for sustained payload release without the need for complex formulations.11 It is crucial that such multicompartmental particles with uniform sizes, structures, and chemical features be generated in a controlled manner via simple, robust, scalable, and low-cost fabrication methods to attain the ideal characteristics desired for the aforementioned applications. Microfluidic techniques have gained substantial attention as a means to fabricate multicompartmental particles (e.g., Janus and core−shell particles). Approaches include emulsion template synthesis,12−15 particle reinjection,16,17 centrifugebased droplet formation,18,19 and flow lithography.16,20 Although these continuous process techniques offer the ability © 2014 American Chemical Society
to rapidly produce spherical and nonspherical multicompartmental particles, several inherent drawbacks exist, including the need for complicated flow control, limited scalability, and a lack of shape controllability. Additionally, although electrohydrodynamic cojetting (EHD) offers the capability to synthesize 3D multicompartmental particles, the resulting particle size distribution tends to be relatively broad, and the technique provides only limited control over particle shape.21 The DeSimone group has pioneered an array of micromolding techniques called particle replication in nonwetting template (PRINT). Although the PRINT method can produce monodisperse 2D particles with excellent controllability over a broad range of sizes,22 the production of 3D particles is limited to predefined mold geometries. While the Xia group has shown a bottom-up fabrication approach for 3D colloidal structures by guided-assembly of prefabricated spheres in confined micromolds, it still has lack of control on the size, shape, and compartmentalization.23 In short, the simple, robust, and scalable fabrication of monodisperse multicompartmental Received: November 10, 2014 Revised: December 22, 2014 Published: December 31, 2014 1328
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Langmuir Scheme 1. Schematic Diagram of Multicompartmental Microparticle Fabrication by Sequential Micromoldinga
a
(A) STEP 1: formation of the primary compartments by surface-tension-induced formation of the photocurable droplets followed by UV-induced polymerization. (B) STEP 2: formation of the secondary compartments by repeating STEP 1.
particles with highly controllable size, shape, and compartmentalization remains challenging. Our approach to addressing such fabrication challenges is based on a simple and robust micromolding technique. The schematic diagram in Scheme 1A (STEP 1) shows that micromolds are filled with photocurable prepolymer solutions. The addition of hydrophobic wetting fluid onto the filled micromolds induces the formation of monodisperse droplets by surface-tension-induced flows.24 Simple photopolymerization of the prepolymer solutions leads to uniform particles in a controlled and cost-efficient manner.25 We have also shown that this simple method can be extended to the production of submicrometer particles and particles of varying sizes (e.g., multiple sizes simultaneously) in a geometrically designed manner.26 This simple technique possesses significant potential for the controlled production of multicompartmental particles in a simple, sequential manner due to the simplicity and robustness arising from the inherent advantages of batch processing. In this work, we report on a sequential micromolding technique for producing monodisperse multicompartmental particles in a simple and controlled manner. Specifically, the droplets used for secondary compartments are formed by repeating STEP 1 and are subsequently assembled with the primary ones, forming monodisperse multicompartmental particles when exposed to UV irradiation, as shown in the schematic diagram in Scheme 1B. The results show that the sequential micromolding method allows for the fabrication of monodisperse bicompartmental particles with a controllable size, shape and chemical composition. This technique can be extended to produce multicompartmental particles with a controllable number of compartments and size ratios through the use of various mold geometries. Moreover, core−shell particles with a controllable number of core regimes can also be readily produced by simply tuning the wettability. Finally, we demonstrate that multicompartmental particles can be utilized for the controlled release of multiple cargo materials. Combined, these results illustrate the simple and robust fabrication of highly monodisperse and complex multi-
compartmental particles in a controlled manner based on sequential micromolding.
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EXPERIMENTAL SECTION
Materials. Poly(ethylene glycol) diacrylate (PEG-DA, Mn = 700), poly(ethylene glycol) (PEG, Mn = 300), trimethylolpropane triacrylate (TMPTA, Mn = 296), n-hexadecane, ethanol, isopropyl alcohol, sulforhodamine B, fluorescein sodium salt, sodium hydroxide, and 2hydroxy-2-methyl-1-phenyl-propan-1-one (Darocur 1173) were purchased from Sigma-Aldrich Chemicals (St. Louis, MO). The surfactant ABIL EM 90 was obtained from Degussa. Fluorescein-labeled (λex 505/λem 515) and rhodamine-labeled (λex 580/ λem 605) colloids were purchased from Invitrogen (Grand Island, NY). The SU-8 photoresist and developer solution were purchased from MicroChem (Westborough, MA). Poly(dimethylsiloxane) (PDMS, Sylgard 184) was obtained from Dow Corning (Midland, MI). Fabrication of the Micromolds. The micromold was fabricated using the conventional soft lithography technique.27 A mixture of polydimethysiloxane (PDMS) prepolymer and its curing agent (10:1 ratio) was poured over a silicon master and cured at 65 °C. After curing, the PDMS replica was peeled off the silicon master. Procedure for Fabricating the Multicompartmental Microparticles. A representative schematic diagram of the procedure used to produce the multicompartmental microparticles is depicted in Scheme 1. For this, we added diluted photocurable PEG-DA solution (10−40 vol %) with ethanol into the micromolds, which formed droplets upon the addition of wetting fluids (n-hexadecane with 2% ABIL EM 90). These droplets were then exposed to UV light to form the primary compartments via photoinduced radical polymerization. The wetting fluids are readily removed simply by pipetting after the curing of the primary compartments. Some residual wetting fluids remain inside micromolds upon this removal step, yet these do not interfere with the secondary compartment fabrication procedure or the retention of the primary compartments. The secondary compartments were formed by repeating the steps for the fabrication of the primary compartments as the primary ones remained in the micromolds. The polymerized particles were washed with excess 2-propanol to remove the wetting fluid. Photopolymerization. To synthesize the polymeric microparticles, droplets of photocurable solution in the molds were exposed to focused UV light (100 W HBO mercury lamp) over a wavelength range of 330−380 nm (UV-2A filter, Nikon, Japan). The estimated UV exposure time of the droplets in the micromolds was typically less than 30 s. 1329
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Langmuir Image Analysis. An inverted fluorescence microscope (TE2000, Nikon, Japan) equipped with a CCD camera (Coolsnap, Photometrics, Tucson, AZ) was used to observe the particle formation and the release profile of the colloids from each compartment in the particles. Image analysis of the particles was performed using the ImageJ (http://rsb.info.nih.gov/ij/) and Image Pro (Media Cybernetics, City, MD) programs. The morphology of the multicompartmental particles was imaged by scanning electron microscopy (SEM; JEOL, JSM7000F, Japan). To characterize the size (diameter) of each compartment, we measured the diameter of projected spheres using bright-field micrographs that are focused at the equatorial (center) plane.
primary compartments. During this process, the primary compartments remained in the micromolds (Figure 1C). At each step, the particles were imaged via bright-field and fluorescence microscopy, and the monodispersity was examined by the coefficient of variation (CV, %). The bright-field fluorescence composite micrograph in Figure 1A shows how the PEG-DA prepolymer solution containing a red fluorescent dye was uniformly loaded into the micromolds. Figure 1B shows the formation of highly uniform polymeric microspheres (primary compartments, denoted as 1 in the inset schematic diagram) from the droplets upon the addition of the hydrophobic wetting fluid and UV-induced photopolymerization. Figure 1C shows the formation of uniform droplets (secondary compartments, denoted by 2 in the inset) upon the addition of PEG-DA monomers and the wetting fluid. Figure 1D shows that simple UV exposure led to the formation of highly uniform, acorn-shaped bicompartmental particles with very high fidelity and that the resulting particles were readily recovered with near-complete yield. In addition, the two compartments did not show signs of detaching after several washing steps under all the conditions examined, presumably due to the formation of interpenetrating networks or further reaction with previously unreacted acrylate moieties remaining in the primary compartment during the polymerization of the second compartment (data not shown). Moreover, this simple sequential technique can be readily extended to various materials and chemistries, as shown in Figure 1E. For example, trimethylolpropane triacrylate (TMPTA) can be used as a hydrophobic secondary compartment to create hydrophilic−hydrophobic particles (i.e., Janus particles), each incorporating two fluorescent dyes with differing solubilities: sulforhodamine B is water-soluble, and fluorescein is oil-soluble. This technique allows for the reliable production of Janus particles with equivalent monodispersity without any modification to the procedure. The size distribution plot shown in Figure 1F clearly indicates that this simple sequential micromolding leads to highly monodisperse bicompartmental particles in a reproducible manner. that is, less than 2.2% CV for the entire population of 1000 particles produced per batch. Finally, Figure 1G shows that the technique can be readily expanded to produce bicompartmental particles over a wide range of compartment size (diameter) ratios. To this end, varying concentrations of the PEG-DA monomer in ethanol were first added to the micromolds. Upon the rapid evaporation of the ethanol and droplet formation by the wetting fluid, UV-cross-linking yielded primary compartments of varying sizes (39−63 μm) that defined the excluded volumes for the secondary compartments (i.e., sizes 68−80 μm). The solid dots in Figure 1G show that these sizes can produce compartment ratios as large as 4.2 in a reproducible manner, as indicated by the consistently small error bars obtained for all the conditions examined. Compared to continuous microfluidic techniques, the results in Figure 1 show that this sequential micromolding technique has several advantages when fabricating multicompartmental particles due to the nature of batch processing. The procedure is simple, with a minimal need for sophisticated equipment or controls, unlike microfluidic techniques, which require a delicate balance of multiphasic flows. Second, this technique allows for the production of well-defined particles with very high fidelity, unlike microfluidic procedures that typically produce incomplete or “bad” particles at the beginning and the end. Third, this sequential method facilitates the
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RESULTS AND DISCUSSION Figure 1 shows that a sequential micromolding technique enables the robust fabrication of highly monodisperse
Figure 1. Bicompartmental microparticles fabricated by sequential micromolding. (A) Composite images showing the photocurable poly(ethylene glycol) diacrylate (PEG-DA) solution loaded into PDMS micromolds. (B) Droplet formation for primary compartments (denoted by 1) by the addition of hydrophobic wetting fluid onto the micromold followed by UV-induced polymerization. (C) Formation of the secondary compartments (denoted by 2) by repeating STEP 1. (D) Collected acorn-shaped bicompartmental particles and (E) Janus particles showing high uniformity. (F) Plot of the size distribution showing the highly monodisperse nature of both compartments shown in Figure 1D. (G) Plot showing the control of the size (diameter) of each compartment and the resulting size ratios obtained from varying concentrations of PEG-DA for the primary compartment. Scale bars represent 100 μm.
bicompartmental particles with precise control over the size and shape anisotropy in a simple manner. For this, we added photocurable poly(ethylene glycol) diacrylate (PEG-DA) solution into the micromolds (Figure 1A), which formed droplets upon the addition of wetting fluids (n-hexadecane with 2% ABIL EM 90) (Figure 1B). These droplets were then exposed to UV light to form the primary compartments via photoinduced radical polymerization. The secondary compartments were formed by simply repeating the steps used for the 1330
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Figure 2. Complex multicompartmental microparticles with controllable sizes and numbers for the primary compartments using simple geometric designs. Composite micrographs and scanning electron microscopy (SEM) images showing the formation from each fabrication procedure and resulting polymeric particles obtained upon UV polymerization. Multicompartmental particles with (A) two identical primary compartments fabricated from tubular molds, (B) two different-sized primary compartments fabricated from tapered molds, (C) three identical primary compartments fabricated from triangular molds, and (D) four identical primary compartments fabricated from cross-shaped molds.
independent control of each compartment, allowing for variable particle functionalities or the encapsulation of different cargo materials (Figure 1E). The capability to simultaneously encapsulate both hydrophilic (e.g., doxorubicin hydrochloride) and hydrophobic (e.g., paclitaxel) molecules in a single particle may be useful for therapeutic applications, including synergistic drug combinations.28,29 Further flexibility may be readily achieved by changing the prepolymer composition and/or using different solidification methods (e.g., thermal polymerization, sol−gel reaction, colloid assembly, and phaseseparation-based solidification).14,30 In summary, the results shown in Figure 1 demonstrate that simple sequential micromolding allows for the fabrication of monodisperse bicompartmental particles with controllable size, shape, and chemistry in a simple and robust manner. One important advantage of our surface-tension-induced droplet micromolding technique is that a wide range of sizes and numbers of microspheres can be readily achieved by simple geometrical designs.16 Exploiting this advantage, we demonstrated that multicompartmental particles could be readily fabricated over a wide range of sizes and numbers of primary compartments (Figure 2). Specifically, the first and second columns of Figure 2 show that PEG-DA prepolymer solution (less than 40% PEG-DA in ethanol) was loaded into polygonal molds with several edges (or branches). The solution volume
decreased as the ethanol evaporated, and the remaining monomer fluid divided into the edges as a result of competing capillary forces between edge regions of a micromold.26 The capillary force is represented by F = γ cos θP, where γ is the surface tension of the PEG-DA, θ is the contact angle of the PEG-DA on the PDMS micromold, and P is projected perimeter of the micromold. Upon the addition of the wetting fluid and UV exposure, various numbers and sizes of monodisperse microspheres were formed, which constituted the primary compartments (STEP 1). Specifically, the second column of Figure 2A and B shows two identical microspheres formed by symmetric tubular shapes and a tapered shape leading to the formation of two microspheres with varying size ratios. The symmetric tubular shape shown in Figure 2A has no variance of the perimeter, resulting in no capillary force gradient, thus leading to formation of two identical droplets. In contrast, an asymmetric design shown in Figure 2B has some variance of the perimeter, generating capillary force gradient between the two edge regions resulting in two different sized droplets at each end. Triangle- and cross-shaped particles led to monodisperse triple and quadruple microspheres, respectively (Figure 2C and D). Next, upon the addition of the PEG-DA and the wetting fluid, the composite micrographs in the third column of Figure 2 show that the droplets for the secondary compartments 1331
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composite micrograph of Figure 3B shows that this simple sequential procedure again yielded highly monodisperse core− shell particles without any significant modification to the fabrication procedure or the requirement of sophisticated controls. Meanwhile, the primary compartment has higher density than the droplet of the secondary compartment when engulfed, leading to sedimentation to the bottom of the droplet then asymmetric shell thickness under the size ranges examined here. Finally, Figure 3C shows that this simple sequential procedure could be readily combined with the geometric controls shown in Figure 2 to produce core−shell particles with a well-defined number of primary compartments. Specifically, dual, triple, and quadruple primary compartments with 20% PEG porogen were fabricated in tubular, triangular, and crossshaped micromolds, respectively. The optical micrographs in Figure 3C show that these primary compartments were entirely engulfed by the secondary compartments, leading to core−shell particles containing one to four primary compartments. Meanwhile, a simple three-phase contact angle measurement (Figure S1, Supporting Information) showed that the core− shell formation (i.e. engulfing) results from significant increase of surface free energy between the primary compartment (cross-linked solid) and the secondary compartment (un-crosslinked liquid). The production of core−shell particles consisting entirely of a hydrophilic polymer is highly challenging and often requires the reinjection of prefabricated particles into the hydrophilic precursor droplets followed by photopolymerization.9 To the best of our knowledge, the results shown in Figure 3 are the first demonstration of the creation of core−shell particles consisting entirely of an identical hydrophilic polymer. Although the microfluidic reinjection technique has recently been shown to produce core−shell particles of similar polarities, this system lacks the ability to control the particle morphology and requires delicate flow control. Unlike the core−shell microparticles comprising immiscible phases, our simple sequential procedure can be applied to novel drug delivery vehicles in which multiple types of hydrophilic payloads or drug molecules must be encapsulated. Additionally, core−shell particles with two different porosities in each compartment can also be used for controlled drug release. Overall, the results in Figure 3 demonstrate that our approach enables the simple and controlled production of core−shell particles. Finally, we demonstrate that the multicompartmental microparticles fabricated by our simple sequential procedure can be utilized for controlled release applications. Figure 4 shows the saponification-based (0.1 N NaOH) degradation of two types of multicompartmental particles: core−shell (Figure 4A) and Janus multicompartmental particles (Figure 4B). To visualize the release profile, we incorporated two fluorescently labeled colloids (2 μm diameter) inside each compartment: rhodamine-labeled colloids (red) in the primary compartment and fluorescein-labeled colloids (green) in the secondary one. The bright-field micrographs in the top row of Figure 4A show that core−shell multicompartmental particles could be designed for controlled release by tunable compositions. Initially, the saponification allowed for the swelling of the shell region (secondary compartment, 20% PEG-DA with 80% porogen) and degradation within 6 h, leading to the release of the green colloids. The remaining core region (primary compartment, 80% PEG-DA with 20% porogen) with denser PEG composition took 10 h for degradation to release the red
formed and combined with the primary compartments in each mold. The composite and SEM images in the fourth column of Figure 2 show that UV exposure led to highly uniform multicompartmental particles with two (A), three (C), and four (D) identical and two different (B) primary compartments of different sizes. Each compartment in the resulting particles was highly monodisperse (CV = 2−3%) under all particle conditions examined. For drug delivery applications, sustained release with tunable kinetics is highly desired. Although complex formulations are commonly required to achieve such ideal profiles, microsized particles may serve as an appropriate design for controlled drug release. The results obtained for controlled multicompartmental particles shown in Figure 2 may provide alternative routes for drug delivery applications in which fine-tuning and release control profiles without complex formulations are highly desired. In short, the results in Figure 2 demonstrate that our simple sequential micromolding technique allows for the simple fabrication of large numbers of monodisperse multicompartmental particles with a controllable size ratio. The reliable fabrication of core−shell microparticles consisting of an entirely hydrophilic polymer composition is challenging.9 Figure 3 shows that the sequential molding
Figure 3. Core−shell multicompartmental particles. (A) Composite images showing the controlled shapes of the multicompartmental particles by varying PEG300 (porogen) concentrations in the primary compartment. (B) Bright-field micrograph of the uniform core−shell multicompartmental particles with a single core and (C) multiple cores with varying numbers (N) of core compartments. Scale bars represent 50 μm.
technique described in this work provides a robust method for the creation of such microparticles. To produce these microparticles, we incorporated varying contents (0−20 vol %) of an inert polyethylene glycol (PEG, Mn = 300) porogen into the primary compartments to control the wettability and mesh size. The composite micrographs in Figure 3A show that the particle morphologies are dramatically changed depending on the PEG content in the primary compartment. Specifically, the PEG content increased the wettability of the droplets used for the secondary compartment onto the primary compartment, allowing for the morphology to be controlled. Importantly, a PEG content greater than 20% allowed for the primary compartment to be entirely engulfed by the droplets for the secondary compartment, leading to the creation of core−shell particles upon UV exposure (Figure 3A, far right). The 1332
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Figure 4. Saponification-based degradation and controlled release using two types of multicompartmental microparticles. (A) Core−shell particles and (B) Janus particles. Two fluorescent-labeled colloidal particles (2 μm diameter) used as model cargos are incorporated in each compartment: rhodamine-labeled colloids (red) in the primary compartments and FITC-labeled colloids (green) in the secondary compartments. Scale bars represent 100 μm.
substantially larger than the ones relevant to biomedical applications, we note that the same sequential micromolding technique can be readily applied to manufacture sub-micrometer sized particles,26 allowing them to be used in in vivo biomedical applications.11 In summary, the results in Figure 4 indicate that our simple sequential molding technique for multicompartmental particles provides a wide range of design parameters for controlled release by tuning compositions of each compartment.
colloids. This sequential profile was further confirmed by the fluorescence micrographs shown in the bottom row of Figure 4A, in which the green colloids in the shell region were released first, followed by the red colloids. In contrast, the bright-field micrographs in Figure 4B show that the Janus multicompartmental particles achieved a simultaneous release profile. Initially, each compartment in the Janus particles was physically segregated, and the size of each compartment increased due to swelling. Each compartment exhibited an identical composition (100% PEG-DA), leading to the simultaneous degradation and release of the encapsulated colloids. The saponification accelerates the cleavage of the ester bond and loosens all of the polymer networks. Nevertheless, the large colloids (in PEG network with ∼1 nm PEG mesh size) were not released until the degrading mesh size was greater than that of the colloids.31,32 Therefore, the low-density PEG network of the shell (green) shown in Figure 4A may have caused an earlier release than in the denser regions (i.e., the core compartments with red colloids in Figure 4A and both compartments in Figure 4B). The results in Figure 4 indicate that the release profiles could be controlled by simply tuning compositions of each compartment. This technique may also be readily extended by programmable release triggered by other external stimuli (e.g., pH, temperature, or osmotic pressure).33,34 Also, other degradation mechanisms by larger molecules such as proteolytic degradation could also be employed, and should initiate and proceed preferentially on the shell layers, protecting the core layers until complete degradation of the shells for further programmable or controlled release.35 While the sizes shown in Figure 4 are
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CONCLUSIONS In this paper, we have demonstrated a simple sequential micromolding method for creating multicompartmental particles with precisely controlled size, shape, compartmentalization, and chemistry. The multicompartmental particles fabricated using our technique were highly monodisperse (CV = 2%) and exhibited very high fidelity. The reliability of production is consistent for the fabrication of other complex microparticles, including multicompartmental, core−shell, and Janus particles with two distinct regions due to the batchprocessing-based nature of the micromolding procedure. Importantly, this batch-processing based technique allows for the fabrication of complex particles in a cost-efficient manner with a minimal need for sophisticated equipment or control algorithms, unlike continuous techniques. Consequently, our method can be readily scaled up for mass production through parallelization. Our results also show that several characteristics of each compartment can be independently controlled by simply tuning various physical parameters, such as the monomer concentration, wettability, and mold geometry. As 1333
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(8) Kim, J.-C. Alginate microspheres incorporating poly(hydroxyethyl acrylate-co-coumaryl acrylate-co-2-ethylhexyl acrylate): Effect of temperature and UV irradiation on FITC-dextran release. Korean J. Chem. Eng. 2014, 31, 1903−1909. (9) Kim, S. H.; Shum, H. C.; Kim, J. W.; Cho, J. C.; Weitz, D. A. Multiple polymersomes for programmed release of multiple components. J. Am. Chem. Soc. 2011, 133, 15165−15171. (10) Luo, R.; Cao, Y.; Shi, P.; Chen, C. H. Near-infrared light responsive multi-compartmental hydrogel particles synthesized through droplets assembly induced by superhydrophobic surface. Small 2014, 10, 4886−4894. (11) Mitragotri, S.; Lahann, J. Physical approaches to biomaterial design. Nat. Mater. 2009, 8, 15−23. (12) Choi, C. H.; Kim, J.; Nam, J. O.; Kang, S. M.; Jeong, S. G.; Lee, C. S. Microfluidic design of complex emulsions. ChemPhysChem 2014, 15, 21−29. (13) Choi, C. H.; Weitz, D. A.; Lee, C. S. One step formation of controllable complex emulsions: from functional particles to simultaneous encapsulation of hydrophilic and hydrophobic agents into desired position. Adv. Mater. 2013, 25, 2536−2541. (14) Nie, Z.; Li, W.; Seo, M.; Xu, S.; Kumacheva, E. Janus and ternary particles generated by microfluidic synthesis: design, synthesis, and self-assembly. J. Am. Chem. Soc. 2006, 128, 9408−9412. (15) Windbergs, M.; Zhao, Y.; Heyman, J.; Weitz, D. A. Biodegradable core−shell carriers for simultaneous encapsulation of synergistic actives. J. Am. Chem. Soc. 2013, 135, 7933−7937. (16) Dendukuri, D.; Pregibon, D. C.; Collins, J.; Hatton, T. A.; Doyle, P. S. Continuous-flow lithography for high-throughput microparticle synthesis. Nat. Mater. 2006, 5, 365−369. (17) Seiffert, S.; Thiele, J.; Abate, A. R.; Weitz, D. A. Smart microgel capsules from macromolecular precursors. J. Am. Chem. Soc. 2010, 132, 6606−6609. (18) Maeda, K.; Onoe, H.; Takinoue, M.; Takeuchi, S. Controlled synthesis of 3D multi-compartmental particles with centrifuge-based microdroplet formation from a multi-barrelled capillary. Adv. Mater. 2012, 24, 1340−1346. (19) Walther, A.; Muller, A. H. Janus particles: synthesis, selfassembly, physical properties, and applications. Chem. Rev. 2013, 113, 5194−5261. (20) Bong, K. W.; Bong, K. T.; Pregibon, D. C.; Doyle, P. S. Hydrodynamic focusing lithography. Angew. Chem., Int. Ed. 2010, 49, 87−90. (21) Bhaskar, S.; Hitt, J.; Chang, S. W.; Lahann, J. Multicompartmental microcylinders. Angew. Chem., Int. Ed. 2009, 48, 4589−4593. (22) Rolland, J. P.; Maynor, B. W.; Euliss, L. E.; Exner, A. E.; Denison, G. M.; DeSimone, J. M. Direct fabrication and harvesting of monodisperse, shape-specific nanobiomaterials. J. Am. Chem. Soc. 2005, 127, 10096−10100. (23) Yin, Y.; Xia, Y. Self-assembly of monodispersed spherical colloids into complex aggregates with well-defined sizes, shapes, and structures. Adv. Mater. 2001, 13, 267−271. (24) Choi, C. H.; Jeong, J. M.; Kang, S. M.; Lee, C. S.; Lee, J. Synthesis of monodispersed microspheres from Laplace pressure induced droplets in micromolds. Adv. Mater. 2012, 24, 5078−5082 5077.. (25) Choi, C. H.; Lee, J.; Yoon, K.; Tripathi, A.; Stone, H. A.; Weitz, D. A.; Lee, C. S. Surface-tension-induced synthesis of complex particles using confined polymeric fluids. Angew. Chem., Int. Ed. 2010, 49, 7748−7752. (26) Choi, C. H.; Kim, J.; Kang, S. M.; Lee, J.; Lee, C. S. Controllable preparation of monodisperse microspheres using geometrically mediated droplet formation in a single mold. Langmuir 2013, 29, 8447−8451. (27) Xia, Y.; Whitesides, G. M. Soft Lithography. Angew. Chem., Int. Ed. 1998, 37, 550−575. (28) Allen, T. M.; Cullis, P. R. Drug delivery systems: Entering the mainstream. Science 2004, 303, 1818−1822.
a result, a wide variety of distinct features can be integrated within each particle in a highly anisotropic manner. Finally, the multicompartmental particles can be used for the controlled release of encapsulated cargo materials, and release profiles can be readily tuned by controlling particle compositions. We envision that our technique may be utilized for the robust fabrication of a wide variety of multicompartmental particles. One example is drug carriers encapsulating multiple components for release in a controlled manner via external stimuli. Moreover, the capability to design particle characteristics should further enable the fabrication of patchy particles (e.g., hydrophobic patches on hydrophilic particles) to permit sites to participate in anisotropic interactions, which may then be used to design novel building blocks for directed selfassembly.
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ASSOCIATED CONTENT
S Supporting Information *
Additional information on three-phase contact angle measurement to examine the engulfing mechanism. This material is available free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Author Contributions §
C.-H.C. and S.-M.K. contributed equally.
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We acknowledge financial support from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (MSIP) (No. NRF-2011-0017322) and by the Space Core Technology Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF2013M1A3A3A02042262).
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DOI: 10.1021/la504404y Langmuir 2015, 31, 1328−1335
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DOI: 10.1021/la504404y Langmuir 2015, 31, 1328−1335
