title: Effects of Pluronic F127-PEG multi-gel-core on the release profile and pharmacodynamics of Exenatide loaded in PLGA microspheres.
abstract: Pluronic F127 and PEG as a multi-gel-core were used to prepare Exenatide-loaded microspheres and store the drug within the microspheres. Also, the sol-gel transition and novel functions of the Pluronic F127-PEG gel core were investigated.Microspheres with a multi-gel-core (GCMs) and without a multi-gel-core (Ms) were compared in terms of the rate of PLGA degradation, therelease kinetics in vitro and the efficacy in KKAy mice. The drug release of GCMs was at a constant rate, and slower than Ms. In addition, after the KKAy mice were given Exenatide for 55days, the blood glucose concentration and HbA1c concentration in the GCMs group were lower than that in the Ms group. The obtained results demonstrated that a single injection of GCMs allowed the mice to maintain a stable blood glucose concentration for two weeks and their body weight was reduced more effectively than that in the Ms group. In addition, GCMs had a longer interval between dosing (two weeks) and a lower dosage(2.4μg/kg) than Bydureon(®) (one week, 33μg/kg). The bioactivity and release of macromolecular Exenatide was improved by the multi-gel-core structure:(1)The hydrophilic Exenatide tended to partition into the PEG chains of F127 and PEG homopolymer, and so it was protected from the organic solvent and vigorous stirring; (2)The macromolecular Exenatide was released both by diffusing through the hydrophilic F127-PEG chains and hydrophobic PLGA.
authors: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 10016, Liaoning, PR China. Electronic address: wpx609612@sina.com.
authors: Puxiu
authors: P
authors: Wang
authors: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 10016, Liaoning, PR China. Electronic address: wangqmoyu@163.com.
authors: Qian
authors: Q
authors: Wang
authors: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 10016, Liaoning, PR China. Electronic address: 267261211@qq.com.
authors: Tianyang
authors: T
authors: Ren
authors: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 10016, Liaoning, PR China. Electronic address: 976724171@qq.com.
authors: Haoyu
authors: H
authors: Gong
authors: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 10016, Liaoning, PR China. Electronic address: 837412837@qq.com.
authors: Jingxin
authors: J
authors: Gou
authors: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 10016, Liaoning, PR China. Electronic address: 55211933@qq.com.
authors: Yu
authors: Y
authors: Zhang
authors: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 10016, Liaoning, PR China. Electronic address: caicuifang@163.com.
authors: Cuifang
authors: C
authors: Cai
authors: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 10016, Liaoning, PR China. Electronic address: tangpharm@126.com.
authors: Xing
authors: X
authors: Tang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D000077270:Exenatide; D005782:Gels / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D010316:Particle Size; D010455:Peptides / Q000494:pharmacology*; D020442:Poloxamer / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013501:Surface-Active Agents / Q000494:pharmacology; D014688:Venoms / Q000494:pharmacology*
chemical_list: D001672:Biocompatible Materials; D005782:Gels; D010455:Peptides; D013501:Surface-Active Agents; D014688:Venoms; D020442:Poloxamer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D000077270:Exenatide