Chuan-Lin Mou

Hole–Shell Microparticles from Controllably Evolved Double Emulsions

Polymeric core–shell microparticles with hollow interiors have great potential for use as microencapsulation systems for controlled load/release, active protection, and confined microreaction. Core–shell structures with solid shells provide effective encapsulation; however, transport of the encapsulated molecule through the shell is more difficult. Addition of holes to the shell can provide more versatility for the microparticles by facilitating mass transport through the shell based on the size or functional selectivity of the holes; this produces microparticles with porous shells for a myriad of uses including controlled capture of particles, controlled release of active molecules and small particles, and removal of pollutants. Additional uses for these microparticles can be achieved through finer control of the holes in the shell: for example, a single, defined hole can provide a very versatile structure for selectively capturing particles for classification and separation, or capturing cells for confined culture. Even more versatility can be obtained through control of the shape of the hollow core: for example, microparticles with a dimple-shaped core are useful for sizeselective capture of colloidal particles, whereas microparticles with a fishbowl-shaped core are more useful for loading objects such as cells and confining a microreaction. Finally, to make these structures fully functional, it is also desirable to control the interfacial properties of the core to enable precise interactions between encapsulated molecules and the solid shell. Colloidal-scale core–shell microparticles with a single hole in the shell are typically made with particle or emulsiontemplate methods: polymerization-induced buckling of silicon drops, freeze-drying solvent-swollen polymeric particles, self-assembly of phase-separated polymers, diffusion-induced escape of monomers or solvents from the microparticles during fabrication, selective polymerization of phase-separated drops, and other means to control the phase behavior of the templates. These microparticles provide excellent performance when sizes less than a few microns are required. By contrast, larger microparticles provide additional versatility when the size requirements are not constrained to very small particles. These microparticles are typically formed using emulsion drops as templates and have sizes of tens of micrometers or larger. Even finer control over the monodispersity of the microparticles is achieved using microfluidic techniques to produce the emulsion templates. The microparticle structure strongly depends on the configuration between the coredrop and shell-drop in the emulsion templates. With the shelldrop partially wetted on the core-drop, organic-biphasic Janus drops produce truncated-sphere-shaped microparticles. With completely wetted core–shell configurations, aqueousbiphasic drops and water-in-oil-in-water (W/O/W) double emulsions respectively produce bowl-shaped and fishbowlshaped microparticles. Surface modification of these microparticles was recently achieved by introducing functional nanoparticles such as SiO2 nanoparticles into the organic phase of the emulsion templates. Complete versatility of the microparticles requires accurate and independent control of the shape and size of both the single-hole and the hollow-core, as well as the functionality of the core surface; this requires precise control of the configurations and interfacial properties of the emulsion templates. However, techniques to achieve this sort of fine control do not exist. Herein, we report a versatile strategy for fabrication of highly controlled hole–shell microparticles with a hollow core and a single, precisely determined hole, and with simultaneous, independent control of the properties of the core interface. W/O/W double emulsions from capillary microfluidics were used as the initial templates for the microparticles. By controlling the composition of the organic middle phase, we varied the adhesion energy DF between the inner drop and outer phase to control the evolution of the emulsions from initial core-shell to the desired acorn-shaped configuration; this produces versatile emulsion templates for controllable fabrication of monodisperse hole-shell microparticles with advanced shapes. Further adjustment of the hole–shell structures can be achieved by changing the size and [*] Dr. W. Wang, M.-J. Zhang, Dr. R. Xie, Dr. X.-J. Ju, C. Yang, C.-L. Mou, Prof. L.-Y. Chu School of Chemical Engineering, Sichuan University Chengdu, Sichuan, 610065 (China) E-mail: chuly@scu.edu.cn Homepage: http://teacher.scu.edu.cn/ftp_teacher0/cly/

Novel cationic pH-responsive poly(N,N-dimethylaminoethyl methacrylate) microcapsules prepared by a microfluidic technique

Novel monodisperse cationic pH-responsive microcapsules are successfully prepared using oil-in-water-in-oil double emulsions as templates by a microfluidic technique in this study. With the use of a double photo-initiation system and the adjustment of pH value of the monomer solution, cross-linked poly(N,N-dimethylaminoethyl methacrylate) (PDM) microcapsules with good sphericity and monodispersity can be effectively fabricated. The obtained microcapsule membranes swell at low pH due to the protonation of N(CH(3))(2) groups in the cross-linked PDM networks. The effects of various preparation parameters, such as pH of the aqueous monomer fluid, concentration of cross-linker, concentration of monomer N,N-dimethylaminoethyl methacrylate (DM) and addition of copolymeric monomer acrylamide (AAm), on the pH-responsive swelling characteristics of PDM microcapsules are systematically studied. The results show that, when the PDM microcapsules are prepared at high pH and with low cross-linking density and low DM monomer concentration, they exhibit high pH-responsive swelling ratios. The addition of AAm in the preparation decreases the swelling ratios of PDM microcapsules. The external temperature has hardly any influence on the swelling ratios of PDM microcapsules when the external pH is less than 7.4. The prepared PDM microcapsules with both biocompatibility and cationic pH-responsive properties are of great potential as drug delivery carriers for tumor therapy. Moreover, the fabrication methodology and results in this study provide valuable guidance for preparation of core-shell microcapsules via free radical polymerization based on synergistic effects of interfacial initiation and initiation in a confined space.

Monodisperse and Fast-Responsive Poly(N-isopropylacrylamide) Microgels with Open-Celled Porous Structure

A simple and efficient method is developed to fabricate monodisperse and fast-responsive poly(N-isopropylacrylamide) (PNIPAM) microgels with open-celled porous structure. First, numerous fine oil droplets are fabricated by homogeneous emulsification method and are then evenly dispersed inside monodisperse PNIPAM microgels as porogens via the combination of microfluidic emulsification and UV-initiated polymerization methods. Subsequently, the embedded fine oil droplets inside the PNIPAM microgels are squeezed out upon stimuli-induced rapid volume shrinkage of the microgels; as a result, a spongelike open-celled porous structure is formed inside the PNIPAM microgels. The open-celled porous structure provides numerous interconnected free channels for the water transferring convectively inward or outward during the volume phase transition process of PNIPAM microgels; therefore, the response rates of the PNIPAM microgels with open-celled porous structure are much faster than that of the normal ones in both thermo-responsive shrinking and swelling processes. Because of the fast-responsive characteristics, the microgels with open-celled porous structure will provide ever better performances in their myriad applications, such as microsensors, microactuators, microvalves, and so on.

Smart microcapsules for direction-specific burst release of hydrophobic drugs

A novel type of monodisperse dual magnetic and thermo-responsive microcapsule, which is composed of a thermo-responsive microgel shell and an eccentric magnetic core as well as an eccentric oil core, is developed for site-specific targeted delivery and direction-specific controlled release of hydrophobic substances. The microcapsules are fabricated with microfluidic-prepared quadruple-component (oil 1 + oil 2)-in-water-in-oil ((O1 + O2)/W/O) double emulsions as templates. The poly(N-isopropylacrylamide) (PNIPAM) microgel shell of the microcapsule can protect the encapsulated hydrophobic drugs at temperatures lower than the lower critical solution temperature (LCST), and achieve the burst release of drugs when the environmental temperature is increased higher than the LCST. The eccentric oil core provides a large inner volume for encapsulation of hydrophobic drug molecules, while the eccentric magnetic core makes the microcapsule able to achieve not only magnetically-guided translational movement for site-specific targeting but also magnetically-guided rotational motion for direction-specific controlled release. The results show that the microcapsules are efficient carriers for site-specific targeted delivery and direction-specific burst release of hydrophobic substances. For the first time our novel microcapsules enable precise “aiming” before “firing”, which is highly desired but was unavailable before.

Trojan‐Horse‐Like Stimuli‐Responsive Microcapsules

Abstract Multicompartment microcapsules, with each compartment protected by a distinct stimuli‐responsive shell for versatile controlled release, are highly desired for developing new‐generation microcarriers. Although many multicompartmental microcapsules have been created, most cannot combine different release styles to achieve flexible programmed sequential release. Here, one‐step template synthesis of controllable Trojan‐horse‐like stimuli‐responsive microcapsules is reported with capsule‐in‐capsule structures from microfluidic quadruple emulsions for diverse programmed sequential release. The nested inner and outer capsule compartments can separately encapsulate different contents, while their two stimuli‐responsive hydrogel shells can individually control the content release from each capsule compartment for versatile sequential release. This is demonstrated by using three types of Trojan‐horse‐like stimuli‐responsive microcapsules, with different combinations of release styles for flexible programmed sequential release. The proposed microcapsules provide novel advanced candidates for developing new‐generation microcarriers for diverse, efficient applications.