Glucose- and temperature-sensitive nanoparticles for insulin delivery

Abstract

Jun-Zi Wu,1 Gareth R Williams,2 He-Yu Li,1 Dongxiu Wang,3 Huanling Wu,1 Shu-De Li,4 Li-Min Zhu1 1College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 2UCL School of Pharmacy, University College London, London, UK; 3Central Laboratory, Environmental Monitoring Center of Kunming, 4School of Basic Medical Sciences, Kunming Medical University, Kunming, People’s Republic of China Abstract: Glucose- and temperature-sensitive polymers of a phenylboronic acid derivative and diethylene glycol dimethacrylate (poly(3-acrylamidophenyl boronic acid-b-diethylene glycol methyl ether methacrylate); p(AAPBA-b-DEGMA)) were prepared by reversible addition–fragmentation chain transfer polymerization. Successful polymerization was evidenced by 1H nuclear magnetic resonance and infrared spectroscopy, and the polymers were further explored in terms of their glass transition temperatures and by gel permeation chromatography (GPC). The materials were found to be temperature sensitive, with lower critical solution temperatures in the region of 12°C–47°C depending on the monomer ratio used for reaction. The polymers could be self-assembled into nanoparticles (NPs), and the zeta potential and size of these particles were determined as a function of temperature and glucose concentration. Subsequently, the optimum NP formulation was loaded with insulin, and the drug release was studied. We found that insulin was easily encapsulated into the p(AAPBA-b-DEGMA) NPs, with a loading capacity of ~15% and encapsulation efficiency of ~70%. Insulin release could be regulated by changes in temperature and glucose concentration. Furthermore, the NPs were non-toxic both in vitro and in vivo. Finally, the efficacy of the formulations at managing blood glucose levels in a murine hyperglycemic diabetes model was studied. The insulin-loaded NPs could reduce blood glucose levels over an extended period of 48 h. Since they are both temperature and glucose sensitive and offer a sustained-release profile, these systems may comprise potent new formulations for insulin delivery. Keywords: diethylene glycol methyl ether methacrylate, 3-acrylamidophenylboronic acid, nanoparticle, thermosensitive, glucose sensitive, insulin delivery

Keywords

• Diethylene glycol dimethacrylate
• 3-acrylamidophenyl boronic acid
• nanoparticle
• thermosensitive
• glucose-sensitive
• insulin delivery.