Chitosan-coated rectangular DNA nanospheres for better outcomes of anti-diabetic drug

Type 2 diabetes is a metabolic disorder in which the patient fails to control the glycemic level due to compromised functioning of pancreatic and cells. The control of these cells is regulated by the extent of incretin peptides (GLP1 and GIP). Performance of these peptides is affected due to the increased degradation by di-peptidyl-peptidase-4 (DPP-4) enzyme in diabetic patients. Vildagliptin (VL) is one of the potential DPP-4 inhibitors and helps in controlling the glycemic level, but to deliver the VL near its site of action (intestine and blood) in a sustained manner is important. For this purpose, we used chitosan (Chit) (cationic polymer) to coat the VL-loaded DNA rectangles (negatively charged) via electrostatic attractions to make Chit-DNA-VL nanospheres. According to our results, nanospheres formulated by this novel approach were uniformed, spherical, and stable with better size control (from 40 to 400nm in diameter). Entrapment efficiency for VL drug was up to 85%. The release of VL was extended up to 12 +/- 5h. From observed incretin and glycemic level, we concluded that the nanospheres efficiently bypassed the gastric acidity improving glycemic control in Db-Db/mouse model. Histological experiments revealed Chit-DNA-VL nanospheres did not cause damage to pancreas associated with the sustained and prolonged release of VL.