Phenylboronic acid-based amphiphilic glycopolymeric nanocarriers for in vivo insulin delivery

July 28, 2017


Phenylboronic acid-based amphiphilic glycopolymeric nanocarriers for in vivo insulin delivery


Honglei Guo, Hongmei Li, Juntao Gao, Guangxi Zhao, Lilu Ling, Bin Wang, Qianqian Guo, Yong Gu, Chaoxing Li




Polymer Chemistry


Diabetes mellitus, a disorder of glucose regulation, is a global burden affecting millions of people across the world. Oral delivery offers a comfortable and physiologically acceptable way to administer insulin to diabetic patients. However, insulin is a protein, which tends to be degraded by enzymes at the gastrointestinal level and shows low bioavailability via an oral route. Here, to investigate a system that is capable of protecting insulin from being damaged and consistently delivering insulin in response to glucose level changes, we prepared amphiphilic glycopolymer poly(D-gluconamidoethyl methacrylate-random-3-acrylamidophenylboronic acid) (p(GAMA-r-AAPBA)), and the glycopolymer assembled into nanoparticles with a narrow size distribution. Insulin was efficiently encapsulated into nanoparticles with a loading capacity up to 11%. An insulin release experiment revealed that the insulin release could be controlled by modifying the composition of glycopolymers and changing the glucose medium. Cell viability showed that p(GAMA-r-AAPBA) nanoparticles had good cytocompatibility. Moreover, a 2-deoxy-[3H] D-glucose (2-DOG) uptake measurement indicated that insulin-loaded nanoparticles had the same physiological function as insulin. A western blot analysis and an immunofluorescence assay revealed that compared to conventional insulin, insulin released from nanoparticles has an identical hypoglycemic mechanism that increased the translocation of glucose transporter type 4 (Glut4) to the plasma membrane. Importantly, there was a significant decrease in blood glucose levels after the oral administration of insulin-loaded p(GAMA-r-AAPBA) nanoparticles to diabetic rats. Therefore, p(GAMA-r-AAPBA) nanoparticles have the potential to be applied as an oral delivery system for proteins and peptides.




Circular dichroism, Secondary structure, Nanostructures, Polymers, Materials