pH-Responsive bio-erodible glipizide loaded PLA@GT-Dextran core-shell microspheres for antidiabetic drug delivery

Abstract

Abstract Hypoglycaemia and fast acting nature of glipizide makes it an effective antidiabetic drug but due to lack of sustainability of glipizide its usage is limited. Here, a pH responsive glipizide loaded PLA (poly (lactic acid)) microspheres were fabricated by emulsion solvent evaporation technique, which were coated with cationic derivative of dextran that exhibited significant pH sensitivity and mucoadhesive property due to presence of positively charged functional group that can readily interact with hydroxyl group present in the mucus lining via polar interaction. The fabricated core-shell microsphere possesses interconnected pores and constriction sites which control the release behavior of loaded glipizide and improve its efficiency. pH-responsive release behavior was evaluated by in-vitro drug release study at three distinct pH of 1.5, 7.4, and 9.2. The physiochemical characterization results confirmed that the glipizide was loaded within PLA microspheres and cationic dextran were present at its surface. The obtained core-shell microspheres possess an average particle size of 17.17 ± 1.33 µm with high drug encapsulation efficiency of 57.47 ± 2.7%. Due to presence of cationic dextran at microsphere`s surface, they possess high hydrophilicity as well as polar interaction with the mucus lining of stomach and also prevent premature release of drug in gastric media as indicated by contact angle measurement and confirmed by in-vitro release study at pH 1.5. A controlled glipizide release of 44.49 ± 11.01% was obtained at pH 9.2 within 48 hours.