Preparation of Microparticles Capable of Glucose-Induced Insulin Release under Physiological Conditions

Abstract

Hydrogen peroxide (H2O2)-sensitive layer-by-layer films were prepared based on combining phenyl boronic acid (PBA)-modified poly(allylamine) (PAH) with shikimic acid (SA)-modified-PAH through boronate ester bonds. These PBA-PAH/SA-PAH multilayer films could be prepared in aqueous solutions at pH 7.4 and 9.0 in the presence of NaCl. It is believed that the electrostatic repulsion between the SA-PAH and PBA-PAH was diminished and the formation of ester bonds between the SA and PBA was promoted in the presence of NaCl. These films readily decomposed in the presence of H2O2 because the boronate ester bonds were cleaved by an oxidation reaction. In addition, SA-PAH/PBA-PAH multilayer films combined with glucose oxidase (GOx) were decomposed in the presence of glucose because GOx catalyzes the oxidation of D-glucose to generate H2O2. The surfaces of CaCO3 microparticles were coated with PAH/GOx/(SA-PAH/PBA-PAH)5 films that absorbed insulin. A 1 mg quantity of these particles released up to 10 μg insulin in the presence 10 mM glucose under physiological conditions.