title: Long-Acting Phospholipid Gel of Exenatide for Long-Term Therapy of Type II Diabetes.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  EXT-loaded phospholipid gel represents a promising controlled release system for long-term therapy of type II diabetes.
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University, No. 17, Section 3, Southern Renmin Road, Chengdu, 610041, China.
authors: Mei
authors: M
authors: Hu
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University, No. 17, Section 3, Southern Renmin Road, Chengdu, 610041, China.
authors: Yu
authors: Y
authors: Zhang
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University, No. 17, Section 3, Southern Renmin Road, Chengdu, 610041, China.
authors: Nanxi
authors: N
authors: Xiang
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University, No. 17, Section 3, Southern Renmin Road, Chengdu, 610041, China.
authors: Ying
authors: Y
authors: Zhong
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University, No. 17, Section 3, Southern Renmin Road, Chengdu, 610041, China.
authors: Tao
authors: T
authors: Gong
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University, No. 17, Section 3, Southern Renmin Road, Chengdu, 610041, China.
authors: Zhi-Rong
authors: ZR
authors: Zhang
authors: 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.
authors: Yao
authors: Y
authors: Fu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D059305:Diet, High-Fat; D004339:Drug Compounding; D004343:Drug Implants; D004355:Drug Stability; D000431:Ethanol / Q000737:chemistry; D000077270:Exenatide; D005782:Gels; D006442:Glycated Hemoglobin / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D010743:Phospholipids / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D013311:Streptozocin; D014280:Triglycerides / Q000737:chemistry; D014688:Venoms / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D004343:Drug Implants; D000431:Ethanol; D000077270:Exenatide; D005782:Gels; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010455:Peptides; D010743:Phospholipids; D013311:Streptozocin; D014280:Triglycerides; D014688:Venoms; C558406:HbA(1c) protein, mouse
keywords: exenatide; gel; phospholipid; sustained-release; type II diabetes