Controlled synthesis of in-situ gold nanoparticles onto chitosan functionalized PLGA nanoparticles for oral insulin delivery.

Chitosan-based nanoparticles (chitosan nanoparticles (ChNps), chitosan gold Nps (ChAuNps), and chitosan gold Nps functionalized with poly lactic-co-glycolic acid (PLGA) (ChAuNps/PLGA)) were prepared as nanocarriers for insulin to improve its oral uptake. The emulsion solvent diffusion method was employed to functionalize the Nps with PLGA. TEM, SEM, DLS, and zeta potential were conducted to characterize the Nps. The morphological analysis confirmed the formation of spherical Nps with hydrodynamic particle sizes of 138±23, 16±2.2, and 50±9.3 nm for ChNps, ChAuNps, and ChAuNps/PLGA, respectively. Zeta potential measurements indicated two types of Nps, regardless of insulin entrapment, positively charged, (ChNps (+36 ± 4.2, +31 ± 2.2mv)) and ChAuNps (+37 ± 4.3, +33 ± 2.5mv) and negatively charged (ChAuNps/PLGA (-31 ± 2.7, -26 ± 2.1 mv)). The in vitro studies were assessed by measuring the entrapment efficiencies (EE%) and the release profiles of insulin at different pH values. EE% for ChNps, ChAuNps, and ChAuNps/PLGA were 97 ± 1.5, 98.4 ± 1.9, and 99 ± 1.2%, respectively. At an acidic medium, a significant level of insulin retention was observed (96 ± 0.08%) for ChAuNps/PLGA. While a high amount was released at higher pH values over an extended period of time. In vivo studies, diabetic rats treated with insulin-loaded Nps had reduced blood glucose level (BGL) (38 ± 2.8, 35 ± 6.5, and 27 ± 5.6%) for ChNps ChAuNps and ChAuNps/PLGA, respectively. The pharmacological availability (PA%) and bioavailability (FR%) for insulin-loaded ChAuNps/PLGA were 15.8 ± 0.71% and 7.7 ± 0.93%, respectively. Altogether, emphasize the role of biocompatible Nps and their efficiency in the convenient delivery of insulin, thus lowering the BGL in a safe condition.