pH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for oral delivery of insulin

Shaoping Sun,1 Na Liang,2 Hiromitsu Yamamoto,3 Yoshiaki Kawashima,3 Fude Cui,4 Pengfei Yan1,5 1Key Laboratory of Chemical Engineering Process and Technology for High-efficiency Conversion, College of Heilongjiang Province (Heilongjiang University), School of Chemistry and Material Science, Heilongjiang University, Harbin, People’s Republic of China; 2College of Chemistry and Chemical Engineering, Harbin Normal University, Harbin, People’s Republic of China; 3School of Pharmaceutical Science, Aichi Gakuin University, Nissin, Japan; 4School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 5Key Laboratory of Functional Inorganic Material Chemistry, Heilongjiang University, Harbin, People’s Republic of China Abstract: This study proposes a new concept of pH-sensitive poly(lactide-co-glycolide) (PLGA) nanoparticle composite microcapsules for oral delivery of insulin. Firstly, insulin–sodium oleate complex was prepared by the hydrophobic ion pairing method and then encapsulated into PLGA nanoparticles by the emulsion solvent diffusion method. In order to reduce the burst release of insulin from PLGA nanoparticles and deliver insulin to specific gastrointestinal regions, hence to enhance bioavailability of insulin, the PLGA nanoparticles were further encapsulated into Eudragit® FS 30D to prepare PLGA nanoparticle composite microcapsules by organic spray-drying method. The preparation was evaluated in vitro and in vivo, and the absorption mechanism was discussed. The in vitro drug release studies revealed that the drug release was pH dependent, and the in vivo results demonstrated that the formulation of PLGA nanoparticle composite microcapsules was an effective candidate for oral insulin delivery. Keywords: sodium oleate, complex, PLGA nanoparticles, Eudragit® FS 30