PLL-alginate and the HPMC-EC hybrid coating over the 3D DNA nanocubes as compact nanoparticles for oral administration

Abstract

Diabetes Type 2 has been quite difficult to treat/manage with elevated fasting/postprandial glycemic levels. Although this metabolic disorder mostly affected older people, recently a big population of young people developed either pre-diabetes or maturity-onset diabetes-mellitus of young (MODY). A Sulphonylurea class of drugs (SUs) has been used for decades to treat/manage diabetes Type 2. However, sustained release formulations of SUs pose a great risk of hypoglycemia due to the burst insulin release with poor control on fasting glycemic levels with pancreatic beta-cells to undergo exhaustion and decreased beta-cells mass with time and decreased the ability to produce/release insulin on chronic stages. This complication augments alpha cells to secrete glucagon due to feedback stimulation. However, Vildagliptin (VI) as a potent DPP-4 inhibitor has incretin-mediated (GLP1 and GIP), and glucose-dependent mechanism of action to stimulate beta-cells postprandial and wreck the secretion of glucagon from alpha cells. It was reported to improve beta-cells mass with time due to hormonal (incretin elevating) mechanism of action and need to decrease the dose after a few years of administration due to improved ability of the pancreas to release insulin. Herein, we report gastro-retentive HPMC-EC/Alg-PLL hybrid coating over the VI loaded 3D DNA-nanocubes through the electrostatic-interactions/solvent-evaporation techniques to make HPMC-EC/Alg-PLL-DNA-VI hybrid nanoparticles. We attained more stable nanoparticles with better size-uniformity (25–50 nm diameter), having a smooth surface with Entrapment efficiency (E.E%) ≈ 95% and sustained VI release up to 18 ± 4 h than our previous studies (35–2500 nm diameter) (E.E% ≈ 74–92% and prolonged VI release ≈ 15 ± 6 h). We observed superior in vivo GLP-1 and glycemic levels. Hence, hybrid nanoparticles being gastro-retentive released VI slowly to the target site (intestine + blood) in vivo without damaging the islets of Langerhans observed from the histological analysis of the pancreas after treatment duration.