Microfluidic Fabrication of Monodisperse Microcapsules for Glucose- Response at Physiological Temperature

Glucose-responsive systems that can change their volumes or other properties in response to glucose concentration, show great potential as drug delivery carriers for controlled release of insulin for diabetes therapy or targeted delivery of anticancer drugs for cancer treatment. In this study, we report on a novel type of monodisperse phenylboronic acid (PBA)-based microcapsules for glucose-response at physiological temperature (about 37 C). Oil-in-water-in-oil (O/W/O) double emulsions generated by microfluidic device are used as templates to synthesize the microcapsules. Poly(Nisopropylacrylamide-co-3-aminophenylboronic acid-co-acrylic acid) (poly(NIPAM-coAAPBA-co-AAc)) hydrogel shell of the microcapsule, with PNIPAM component as actuator and AAPBA component as glucose sensor, shows good responsivity to the blood glucose concentration at physiological temperature. To obtain the maximum swelling volume transition of the microcapsule at 37 C, the molar ratio of AAc in the hydrogel shell is selected as 2.4 mol%. At physiological temperature, Glucoseresponsive microcapsules prepared with 2.4 mol% AAc exhibit reversible and repeated swelling/shrinking responses to glucose concentration changes within the physiological blood glucose concentration range (0.4~3.0 g/L). The glucose-sensitive swelling/deswelling behaviors show good reproducibility with glucose concentration repeatedly varying between 0.4 g/L and 3.0 g/L. Rhodamine B and fluoresceinisothiocyanate-labeled insulin are used as model molecules and model drugs to demonstrate the potential application of the microcapsules for glucose-responsive controlled release. The microcapsules provide a promising and feasible model for developing glucose-responsive sensors and self-regulated delivery systems for diabetes and cancer therapy. Moreover, the microfluidic fabrication approach and research results presented here provide valuable guidance for the design and fabrication of monodisperse glucose-responsive microcapsules. 1) Graduate Student 2) Assistant Professor 3) Professor