NANOENCAPSULATION AUGMENTS RELEASE EFFICACY AND GLUCOSE TOLERANCE OF 14-DEOXY, 11, 12-DIDEHYDRO ANDROGRAPHOLIDE LOADED POLYCAPROLACTONE NANOPARTICLES IN STREPTOZOTOCIN-NICOTINAMIDE INDUCED TYPE 2 DIABETES

Objective: This study was designed to study the release efficacy and glucose tolerance of 14-deoxy, 11, 12-didehydroandrographolide loaded polycaprolactone nanoparticles in streptozotocin-nicotinamide induced type 2 diabetes. Methods: Biodegradable polymer based novel drug delivery systems had brought a considerable attention to improve therapeutic efficacy and bioavailability of various drugs. In this study, 14-deoxy-11, 12-didehydroandrographolide (sparingly water soluble) loaded polycaprolactone (nano-DDA) was synthesized using polyvinyl alcohol and tween20 as surfactants. MTT assay was performed to analyse the cytotoxicity of both the formulations on L6 myoblasts. Free DDA and nano-DDA were administered orally to the streptozotocin-nicotinamide induced experimental diabetic rats for 45d. Oral glucose tolerance test (OGTT) was carried out at the end of the study. After one week washout period, animals were administered with free and nano-DDA and release efficacy of DDA from polymer matrix and concentration of glucose were analysed. Results: MTT assay revealed that nano-DDA prepared using tween-20 as a surfactant elicited cytotoxicity towards L6 myoblasts, whereas nano-DDA prepared using polyvinyl alcohol as a surfactant remained non-toxic till 10µM. OGTT studies revealed an initial increase of glucose at 30 min followed by a progressive decrease in the glucose level. In rat plasma, a gradual decrease in glucose level was observed up to 32h (139 mg/dl) for free DDA, whereas nano-DDA exhibited a major decrease in glucose concentration at 32h (115 mg/dl) which continued even after 48h (117 mg/dl). Conclusion: A slow and sustained release of DDA from the polymer matrix substantiated that nanoencapsulation enhanced the oral bioavailability of DDA which resulted in decreasing the concentration of glucose which could be due to the pronounced antihyperglycemic activity of nano-DDA over free DDA