Evaluation of chitosan/eudragit hybrid coating over cubic DNA nanospheres with superior stability and therapeutic outcomes

Abstract

© 2019 Elsevier B.V. Diabetes T2 is a quite devastating metabolic disorder recently affecting both young as well as old patients who have a failure in maintaining their glycemic-levels postprandial. The sulphonylurea class of drugs further increase the beta-cells exhaustion leading to decreased ability of beta-cells to release insulin in-turn causing feedback activation of alpha-cells to release glucagon. These complications arisen in the T2 diabetics further complicate the management of the disease in an irreversible way. However DPP-4 inhibitors such as Vildagliptin (VL)not only causes incretin-mediated (GLP1 & GIP), glucose-dependent beta-cells activation postprandial, with decreased evidence of beta-cells exhaustion but also suppress glucagon secretion that further decrease the load on beta-cells to maintain glycemic levels. To effectively inhibit the di-peptidyl-peptidase-4 (DPP-4)enzyme and elevate the postprandial incretin-levels targeted sustained release vildagliptin nano-formulation was required which may reach the large intestine as well as to blood more effectively with increased potential of DPP-4 inhibition round the clock with improved glycemic levels. For this purpose, gastro-resistant chitosan/eudragit (cationic polymers)hybrid coating was applied around the VL loaded DNA cubes (negatively charged)through the electrostatic interactions to make Chit/Eud-DNA-VL nanospheres. Hybrid coating technique provided better size uniformity (35–120 nm diameter), stability and attainment of firm circular surface topology with Entrapment efficiency up to 92% and extended drug release up to 18 ± 2 h, as compared to our previously reported methods (40–2000 nm in diameter, Encapsulation efficiency 75–85% and extended drug release up to 12 ± 5 h). In vivo experiments also revealed the improved GLP-1 levels in the blood and glycemic control. So hybrid nanoparticles showed better gastric-resistance and prolonged VL release at the target site in our in vivo experiments with no damage to the pancreatic cells confirmed through post-treatment histological examination.