Preparation of uniform-sized exenatide-loaded PLGA microspheres as long-effective release system with high encapsulation efficiency and bio-stability.
Exenatide-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres hold great potential as a drug delivery system to treat type 2 diabetes mellitus (T2DM) because they can overcome the shortcoming of exenatide's short half-life and realize sustained efficacy. However, conventional preparation methods often lead to microspheres with a broad size distribution, which in turn would cause poor preparation repeatability, drug efficacy and so forth. In this study, we used Shirasu Porous Glass (SPG) premix membrane emulsification technique characterized with high trans-membrane flux and size controllability to prepare uniform-sized PLGA microspheres. By optimizing trans-membrane pressure and PVA concentration in external aqueous phase, uniform-sized PLGA microspheres with large size (around 20μm) were successfully obtained. To achieve high encapsulation efficiency (EE) and improve in vitro release behavior, we have carefully examined the process parameters. Our results show that using ultrasonication to form primary emulsion, microspheres with high EE were easily obtained, but the rate of in vitro release was very slow. Instead, high EE and appropriate in vitro release were achieved when homogenization with optimized time and speed were employed. Besides, we also systematically investigated the effect of formulations on loading efficiency (LE) as well as the relationship between the resultant size of the microspheres and pore size of the membrane. Finally, through RP-HPLC and CD spectra analysis, we have demonstrated that the bio-stability of exenatide in microspheres was preserved during the preparation process.
National Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production and Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Feng
F
Qi
Jie
J
Wu
Qingze
Q
Fan
Fan
F
He
Guifang
G
Tian
Tingyuan
T
Yang
Guanghui
G
Ma
Zhiguo
Z
Su
D002626:Chemistry, Pharmaceutical; D002942:Circular Dichroism; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D000077270:Exenatide; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D019344:Lactic Acid; D008863:Microspheres; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011142:Polyvinyl Alcohol; D011312:Pressure; D014688:Venoms / Q000008:administration & dosage*
D003692:Delayed-Action Preparations; D004655:Emulsions; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011142:Polyvinyl Alcohol; D000077270:Exenatide
Exenatide; In vitro release; Narrow size distribution; PLGA microspheres; Premix membrane emulsification