The drug release kinetic and biocompatibility of biocompatible polysaccharide depot for delivery of type II diabetes drug

Poly(lactic-co-glycolide) (PLGA) microspheres have been investigated for a long time as a protein/peptide delivery depot, and some products were already commercialized. However, recent publications have report about their disadvantages in the long term delivery of protein/peptide drugs such as the denaturation, aggregation, and deamidation of protein/peptide drug. The phenomena are induced by proton generated from the hydrolysis of ester linkages in PLGA. It is well known that an acidic condition facilitates the denaturation, aggregation, and deamidation. Therefore, the development of new protein/peptide delivery depot is necessary. In this study, pullulan acetate microsphere (PAM) was inspected as a depot for long term delivery of exendin-4 which is a drug for type II diabetes. The mean particle size of PAM ranged from 35 to 110 mm, as determined by SEM. Their shapes were regular and spherical, as visualized via SEM photographs. The encapsulation efficinecy of exenatide in PAMs was 69.1%, 80.4%, and 90.3% in PAM1, PAM2, and PAM3, respectively. And the exenatide release from PAMs was shown a sustained release profile for 21 days. We identified a biocompatibility of PAM through the tissue reaction by H&E staining. On the basis of these results, the microspheres may give an idea for development of new protein/peptide depot in long term delivery.