Amphiphilic glycopolymer nanoparticles as vehicles for nasal delivery of peptides and proteins.
writer：Chao Zheng, Xinge Zhang*, Qianqian, Guo, Chaoxing Li, Zhengpu Zhang*
keywords：nasal delivery, nanoparticles
source：期刊
specific source：European Journal of Pharmaceutical Science, 2013, in press.
Issue time：2013年
The application of proteins and peptides is hampered by their rapid clearance in liver and other body tissues by proteolytic enzymes, so they are difficult to administer except by the injection. To explore phenylboronic acid-functionalized glycopolymeric nanoparticles as effective carriers for the nasal delivery of proteins and peptides, a novel amphiphilic glycopolymer poly(2-lactobionamidoethyl methacrylate-random-3-acrylamidophenylboronic acid) (p(LAMA-r-AAPBA)) was prepared. p(LAMA-r-AAPBA) could assemble into the nanoparticles with narrow size distribution. Insulin, as a model drug, was efficiently encapsulated within the nanoparticles, and loading capacity was up to 12%. The in vitro study revealed that the release of insulin could be controlled by modifying the composition of glycopolymers. Cell viability showed that p(LAMA-r-AAPBA) nanoparticles had good cytocompatibility. Moreover, the mechanism of nanoparticle internalization into Calu-3 cells was a combination mechanism of clathrin-mediated endocytosis and lipid raft/caveolae-mediated endocytosis. Importantly, there was a significant decrease in the blood glucose levels after the nasal administration of p(LAMA-r-AAPBA) nanoparticles to diabetic rats. Therefore, p(LAMA-r-AAPBA) glycopolymers have a potential application for nasal delivery of proteins and peptides.