Design, optimization, and in-vivo performance of glipizide-loaded O-carboxymethyl chitosan nanoparticles in insulin resistant/type 2 diabetic rat model

Abstract

Developing an oral nano-based delivery system for diabetes combines the desirable patient compliance of oral delivery with the tunable physicochemical features of nano-systems. Glipizide (GPZ) is a second-generation sulfonylurea drug used for treating type-2 diabetes (T2D). GPZ suffers from poor solubility and a short half-life (2–4 h). GPZ was loaded into O-Carboxymethyl chitosan (O-CMC) nanoparticles (NPs) to obtain a prolonged antidiabetic effect and monitor their effects on different T2D-related biomarkers. Optimized GPZ-O-CMC-NPs showed a particle size of 216 ± 2.5 nm, a zeta potential of −14.2 ± 2.1 mV, and an entrapment efficiency of 80.7 ± 0.8%. Fourier transform-infrared (FTIR) spectroscopy, Differential scanning calorimetry (DSC), and Transmission electron microscopy (TEM) were performed. GPZ-O-CMC-NPs had a superior and prolonged release profile than that of marketed and pure GPZ. Treatment with GPZ-O-CMC-NPs had a more significant impact (P < 0.05) on serum glucose, insulin, lipid profile (3–4 folds), oxidative stress markers (2–3 folds), and inflammatory cytokines (2.5–3.5 folds) than marketed or pure GPZ. These findings corroborate the potential benefits of GPZ-O-CMC-NPs for treating T2D.