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Objective: The present study was designed to evaluate the bioavailability of nano encapsulated DDA (nano-DDA) in experimental diabetic rats. Methods:Polycaprolactone was used as a polymer to encapsulate 14-deoxy-11, 12-didehydroandrographolide (DDA) using solvent evaporation technique in order to improvise the bioavailability of the drug. Male albino wistar rats were induced with single intraperitoneal injection of nicotinamide (110 mg/kg) followed by streptozotocin (45 mg/kg) to induce experimental diabetes. Free DDA and nano-DDA were orally administered to the experimental diabetic rats for 45d and blood glucose level was monitored periodically. After one week washout period, free DDA and nano-DDA were orally administered to the rats and blood samples were collected at predetermined intervals. Plasma concentration of DDA was determined by highperformance liquid chromatography (HPLC). Pharmacokinetic analysis was carried out to determine the oral bioavailability.Results: 50 mg of nanoparticle-containing 9.4 mg of DDA exhibited a significant decrease in blood glucose level (105.6±2.99 mg/dL), on par with the free drug administered (50 mg/kg). The nano-DDA accomplished a significant increase in Cmax (961.7±8.78ng) and area under the curve (AUC) (2631±6.98 h X ng/ml) than free DDA. A significant increase in the oral bioavailability was witnessed for nano-DDA (absolute bioavailability% = 34.94±0.231%), which was 10.8 times higher than the free DDA (3.234±0.062 %) and substantiated a slow and sustained drug release from the polymer matrix. Conclusion:Our results substantiated that nanoencapsulation of DDA, enhanced the oral bioavailability of DDA than the free drug in vivo. Nano-DDA can thus serve as a bioactive molecule in the quest for new antidiabetic nano drug discovery.

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