DDA LOADED PCL NANOPARTICLES ENHANCES THE ORAL BIOAVAILABILITY OF DDA IN DIABETES INDUCED EXPERIMENTAL RATS
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 high-performance 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 (105.6Â±2.99 mg/dL), on par with the free drug administered (50 mg/kg). The nano-DDA accomplished a significant increase in Cmax (961.7Â±8.78ng) and area under the curve (AUC) (2631Â±6.98 h X ng/ml) than free DDA. A significant increase in the oral bioavailability was witnessed for nano-DDA (absolute bioavailability% = 34.94Â±0.231%), which was 10.8 times higher than the free DDA (3.234Â±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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