Orally deliverable nanoformulation of liraglutide against model type 2 diabetic rat

The present study was designed to evaluate the hypoglycemic effect of nanoparticle based drug delivery system of liraglutide loaded in Poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) upon oral delivery in experimentally induced type 2 diabetes mellitus in Wistar rats. NPs were synthesized using double emulsion solvent evaporation method. Physiochemical characterization of NPs revealed small particle size of 159.25 +/- 24.46 nm with 75 +/- 7.8% liraglutide encapsulation efficiency and 7 +/- 1% as liraglutide loading efficiency. The NPs were also studied for in vitro release study and stability studies in various gastrointestinal fluid pH conditions which demonstrated the stability of NPs under these conditions. In-vivo model in wistar rats induced by high fat diet (HFD) along with Streptozotocin (STZ) were treated with liraglutide NPs for 8 weeks at two doses (75 and 150 mu g/kg, orally). The rats were monitored for various biochemical and physiological parameters at regular intervals i.e. baseline before initiation of the experiment, at the 1st, 5th, and 9th week of STZ administration. Further in vivo study showed alleviation of HFD-STZ induced diabetes mellitus as evident from the reduction in biochemical parameters like blood glucose (both fasting and post prandial blood glucose), HbA1c, fructosamine levels, serum triglycerides, serum total cholesterol. Physiological parameters such as body weight and food intake were also in support of the data. Moreover, liraglutide NPs demonstrated hypoglycemic activity by significantly increasing the insulin secretion in diabetic rats. To the best of our knowledge, we for the first time proposing the orally deliverable NPs of liraglutide that ameliorates HFD-STZ induced diabetes mellitus effectively as compared to conventional liraglutide.