Synthesis of Y-Shaped Copolymers Containing Phenylborate Ester and Biodegradable Poly(lactic acid) Blocks and Their GlucoseSensitive Behavior for Controlled Insulin Release

This study is devoted to developing amphiphilic, biodegradable, Y-shaped block polymers, which can self-assemble to form nanoparticles, as a glucose-sensitive drug carrier. Y-shaped poly(ethylene glycol)-block-[poly(lactic acid)-block-poly (2-phenylborate esters-1,3-dioxane-5-methyl) methylacrylate)](2) (MPEG-(PLA-block-PPBDMMA)(2)) polymers are constructed via a combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP) with MPEG-(OH)(2), having double initiation endings, as starting material. These Y-shaped block polymers can disperse in an aqueous medium and self-assemble into micellar aggregates with a spherical core-shell structure. Dynamic laser scattering (DLS), zeta potential measurements, and transmission electron microscopy (TEM) show the solution properties of these polymeric micelles with or without insulin loading. Compared with MPEG-PLA-block-PPBDMMA linear polymer, in vitro insulin release at different glucose concentrations, revealed by the fluorescence technique, shows that the studied Y-shaped polymers have intelligent glucose-concentration-dependent manner of insulin release at pH 7.4 and 37 degrees C. The bulk swelling phenomenon of the polymeric micelles formed from the Y-shaped polymers is detected by DLS in the process of their glucose-responsiveness. Such a Y-shaped glucose-responsive polymer is a promising candidate that holds great potential in the treatment of diabetes.