ポリの合成（<em> N</em> -isopropylacrylamide）異方性熱応答性および有機性/親水性ローディング機能のためのヤヌスMicrohydrogels

Hydrogels are a network of hydrophilic polymer chains.¹ An increasing amount of research in the field of hydrogels has promoted significant advances and revealed their similarity to biological tissues; the properties of hydrogels allow the uptake of large amounts of water while maintaining their structure. Environmentally responsive hydrogels have also been studied extensively because of their ability to swell or shrink reversibly in response to external stimuli.² Several triggers, including temperature,^3-5 pH,^6,7 light,^8,9 electric fields,^10,11 and specific molecules, such as glucose,^12,13 have been suggested to control the geometric shape of hydrogels. Among the many environmentally responsive hydrogels currently available, poly(N-isopropylacrylamide) (PNIPAAm), a well-known thermo-responsive hydrogel, exhibits volume shrinkage above a low critical solution temperature (LCST) of 32 °C.¹⁴ A recent study by Sasaki et al.¹⁵ reported the intriguing liquid-liquid phase separation of supersaturated NIPAAm, which is the monomer of PNIPAAm. According to this report, supersaturated NIPAAm was dissolved with a 10-fold molar excess of H₂O, and soon after, the solution separated into two liquid phases when allows to stand at a temperature above 25 °C; by contrast, dilute NIPAAm was dissolved homogeneously under the same conditions.

Microparticles made of environmentally responsive hydrogels are fascinating candidates for application in drug delivery,^16,17 catalysis,¹⁸ sensing,^19,20 and photonics.²¹ Traditional synthetic methods including emulsion polymerization, are used to produce hydrogel microparticles with polydispersity.^22,23 However, certain applications require microparticles with a narrow size distribution, for example, to stabilize the pharmacokinetics of drug delivery.²⁴ Irregularly shaped or polydisperse embolic microparticles aggregate proximally into clusters, leading to chronic inflammatory responses in embolic particles for cancer therapeutic treatment.^25,26

The microfluidic approach is at the forefront of research as a means of fabricating micro-sized particles with narrow size distributions and complex shapes.^27-31 The advantages of fabricating microparticles in the microfluidic device are predicated by the small characteristic length of the microfluidic device, which results in a low Reynolds number. In contrast to traditional bulk emulsification where drops are formed in parallel, microdroplets produced in microfluidic devices are generated in series and subsequently polymerized into microparticles upon exposure to UV irradiation. The fundamental principle of droplet formation using a microfluidic device is balance between the interfacial tension and the shear force of the sheath fluid acting on the core fluid.

Despite the obvious advantages of microfluidic fabrication of droplets/particles, Janus droplets/particles consisting of the same base material are rarely reported because the internal morphology of these droplets/particles is generally disturbed by the diffusion and perturbation of the core fluids. To circumvent this intrinsic limitation, two groups recently reported the preparation of the Janus microparticles by employing heat-induced phase separation of colloidal nanoparticles and UV-directed phase separation.^32,33

To this end, we report a microfluidic approach to synthesize Janus microhydrogels entirely composed of a single base material and obtain a product with clearly compartmentalized morphology. Our approach is based on the primary concept of liquid-liquid phase separation of supersaturated NIPAAm monomer. The resulting Janus microhydrogels were found to possess unique properties including anisotropic thermo-responsiveness and organophilic/hydrophilic loading capability.