In vitro and in vivo sustained release of exenatide from vesicular phospholipid gels for type II diabetes

Abstract

Diabetes is a chronic disease that requires daily treatment to maintain a stable blood glucose level. Sustained-release formulations can thus benefit the treatment of diabetes by reducing the repeated administration of therapeutics. Our study aimed to develop a sustained-release platform for exenatide that is biocompatible and capable of mass production. Vesicular phospholipid gels (VPGs) are semisolid phospholipid dispersions with controlled release profiles. Exenatide-VPGs prepared via simple magnetic stirring showed excellent biocompatibility with an average particle size of about 15 μm after redispersion. VPGs were shown to achieve sustained release for up to 21 days in vitro with no obvious burst effect. The in vivo release study showed that VPGs sustained the release of the exenatide for up to 11 days. Moreover, after subcutaneous injection of the exenatide-VPGs in the diabetic rats, the hypoglycemic effect lasted for 10 days compared with exenatide solution. In sum, the exenatide-VPGs system represents a promising sustained-release formulation for exenatide with a long-acting therapeutic efficacy in vivo.

Keywords: Exenatide; sustained-release formulation; type II diabetes; vesicular phospholipid gels.