title: Mechanistic studies for monodisperse exenatide-loaded PLGA microspheres prepared by different methods based on SPG membrane emulsification.
abstract: Poly(DL-lactic-co-glycolic acid) (PLGA) microspheres have been widely prepared by many methods, including solvent evaporation, solvent extraction and the co-solvent method. However, very few studies have compared the properties of microspheres fabricated by these methods. This is partly because the broad size distribution of the resultant particles severely complicates the analysis and affects the reliability of the comparison. To this end, uniform-sized PLGA microspheres have been prepared by Shirasu porous glass premix membrane emulsification and used to encapsulate exenatide, a drug for treating Type 2 diabetes. Based on this technique, the influences on the properties of microspheres fabricated by the aforementioned three methods were intensively investigated, including in vitro release, degradation and pharmacology. We found that these microspheres presented totally different release behaviors in vitro and in vivo, but exhibited a similar trend of PLGA degradation. Moreover, the internal structural evolution visually demonstrated these release behaviors. We selected for further examination the microsphere prepared by solvent evaporation because of its constant release rate, and explored its pharmacodynamics, histology, etc., in more detail. This microsphere when injected once showed equivalent efficacy to that of twice-daily injections of exenatide with no inflammatory response.
authors: State Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People's Republic of China; University of the Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors: Feng
authors: F
authors: Qi
authors: State Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
authors: Jie
authors: J
authors: Wu
authors: State Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
authors: Tingyuan
authors: T
authors: Yang
authors: State Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People's Republic of China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, People's Republic of China. Electronic address: ghma@ipe.ac.cn.
authors: Guanghui
authors: G
authors: Ma
authors: State Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, People's Republic of China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, People's Republic of China.
authors: Zhiguo
authors: Z
authors: Su
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D004655:Emulsions; D005898:Glass / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008422:Materials Testing; D008567:Membranes, Artificial; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003692:Delayed-Action Preparations; D004655:Emulsions; D007004:Hypoglycemic Agents; D008567:Membranes, Artificial; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Controlled release; Exenatide; Microsphere; PLGA; SPG membrane emulsification