Photo-regulated insulin delivery from glucose-responsive core-shell microspheres prepared by two-step high-speed shear-emulsions

Abstract

Event Abstract Back to Event Photo-regulated insulin delivery from glucose-responsive core-shell microspheres prepared by two-step high-speed shear-emulsions Ruixue Yin1, Kemin Wang2, Hongbo Zhang1*, Wenjun Zhang3 and Nan Zhang2 1 East China University of Science and Technology, Mechanical and power engineering, China 2 Changzhou University, Materials science and engineering, China 3 University of Saskatchewan, Biomedical engineering, Canada Introduction: Traditional multi-dose subcutaneous injection for diabetes patients too often leads to inadequate glycemic control accompanied by pain. Recently, some implantable insulin delivery devices have been developed to release insulin in response to the blood glucose level [1],[2]. Considering the body weight and insulin resistance of patients, more attention should be paid on further real-time control of insulin release when such insulin devices are implanted inside the body, especially for basal insulin release control. Hence, core-shell microspheres with glucose-responsive core and photo-responsive shell are fabricated to achieve real-time photo-regulated insulin delivery accompanied by glucose-responsive insulin release according to blood glucose level changes. Materials: Concanavalin A (Con A), dextran, poly (ethylene glycol) dimethacrylate (PEGDMA) and bovine insulin were purchased from Yuanye Biotech.Co. (Shanghai, China). Glycidyl methacrylated dextran (Dex-G) and cinnamic acid modified dextran (Dex-C) were synthesized according to literatures[3],[4]. Methods: The core-shell microspheres were fabricated by a two-step high-speed shear-emulsion method. Briefly, a mixture of Dex-G, Con A, insulin and PEGDMA was added dropwise to cyclohexane with span 80 as stabilizer, stirring at 5,000 rpm for 2 min, followed by the addition of initiator. After further hardening and standing, the solid spheres were collected, which were then dispersed in Dex-C/ dichloromethane solution and added into polyvinyl alcohol solution to obtain core-shell microspheres using solid-in-oil-in-water method. Results: The morphology of core-shell microspheres was more regular compared with the core layer (see Fig. 1a and 1c). The diameters of core-layer and core-shell microspheres were 2.78 and 5.23 μm, respectively, with a borad distribution range of the core-shell spheres (see Fig. 1b and 1d). TGA and DTG curves ( see Fig. 1e and 1f) illustrated a higher decomposition temperature of core-shell microspheres. Insulin release behavior in response to step changes in glucose levels in five cycles and under real-time photo-irradiation (λ > 300 nm) were illustrated in Fig. 2, indicating an increase-decrease trend of insulin concentration in response to glucose level changes and a reduced insulin release amount after a small dose of UV irradiation. Discussion: The shape and size of core layer was mainly affected by the shear rate and the amount of crosslinker, while the formation of core-shell microspheres was more stable. The successful fabrication of core-shell microspheres was proved by not only the enlarged diameter of microspheres from 2.78 μm to 5.23 μm, but also the enhanced thermal stability of core-shell microspheres, owing to the introduction of Dex-C in the shell layer with higher decomposition temperature than Dex-G. In vitro insulin release test indicated that the obtained core-shell microspheres could release insulin in a pulsatile mode according to glucose concentration changes, and the release behavior could be regulated by real-time photo-irradiation. Conclusion: Core-shell microspheres are fabricated by a simple two-step high speed-emulsion method. With the combination of glucose-responsive insulin release behavior and real-time photo-regulation of basal insulin release, the obtained microspheres have great potential to be used for diabetes patients. National Natural Science Foundation of China (21404038); The Postdoctoral Science Foundation of China (2014M551345)