Mei Hu1, Yu Zhang1, Nanxi Xiang1, Ying Zhong1, Tao Gong1, Zhi-Rong Zhang1, Yao Fu2. 1. Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University, No. 17, Section 3, Southern Renmin Road, Chengdu, 610041, China. 2. Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University, No. 17, Section 3, Southern Renmin Road, Chengdu, 610041, China. yfu4@scu.edu.cn.
Abstract
PURPOSE: This study aimed to develop a sustained-release formulation of exenatide (EXT) for the long-term therapeutic efficacy in the treatment of type II diabetes. METHODS: In this study, we present an injectable phospholipid gel by mixing biocompatible phospholipid S100, medium chain triglyceride (MCT) with 85% (w/w) ethanol. A systemic pre-formulation study has been carried out to improve the stability of EXT during formulation fabrication. With the optimized formulation, the pharmacokinetic profiles in rats were studied and two diabetic animal models were employed to evaluate the therapeutic effect of EXT phospholipid gel via a single subcutaneous injection versus repeated injections of normal saline and EXT solution. RESULTS: With optimized formulation, sustained release of exenatide in vivo for over three consecutive weeks was observed after one single subcutaneous injection. Moreover, the pharmacodynamic study in two diabetic models justified that the gel formulation displayed a comparable hypoglycemic effect and controlled blood glucose level compared with exenatide solution treated group. CONCLUSIONS: EXT-loaded phospholipid gel represents a promising controlled release system for long-term therapy of type II diabetes.
PURPOSE: This study aimed to develop a sustained-release formulation of exenatide (EXT) for the long-term therapeutic efficacy in the treatment of type II diabetes. METHODS: In this study, we present an injectable phospholipid gel by mixing biocompatible phospholipid S100, medium chain triglyceride (MCT) with 85% (w/w) ethanol. A systemic pre-formulation study has been carried out to improve the stability of EXT during formulation fabrication. With the optimized formulation, the pharmacokinetic profiles in rats were studied and two diabetic animal models were employed to evaluate the therapeutic effect of EXTphospholipid gel via a single subcutaneous injection versus repeated injections of normal saline and EXT solution. RESULTS: With optimized formulation, sustained release of exenatide in vivo for over three consecutive weeks was observed after one single subcutaneous injection. Moreover, the pharmacodynamic study in two diabetic models justified that the gel formulation displayed a comparable hypoglycemic effect and controlled blood glucose level compared with exenatide solution treated group. CONCLUSIONS:EXT-loaded phospholipid gel represents a promising controlled release system for long-term therapy of type II diabetes.
Entities:
Keywords:
exenatide; gel; phospholipid; sustained-release; type II diabetes
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