Dda Loaded PCL Nanoparticles Enhances the Oral Bioavailability of Dda in Diabetes Induced Experimental Rats

Abstract

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.

Oral empagliflozin-loaded tri-layer core-sheath fibers fabricated using tri-axial electrospinning: Enhanced in vitro and in vivo antidiabetic performance

“…In a study, bioavailability has been increased 3.6-fold in a micelle formulation prepared with PLA in rats (Mu et al, 2010). A significant increase in the oral bioavailability has been found for didehydroandrographolideloaded PCL nanoparticles, which was 10.8-fold higher than the free DDA and demonstrated a slow and sustained drug release from the polymer matrix in STZ/NA-induced diabetic rats (Nagalakshmi, K., Sujatha, S., Alwin, D., 2017). In the current study, the bioavailability was improved by ~ 4.8-fold by loading EM to tri-layer PCL/PLA/PMMA fibers compared to EM-powder.…”

Antibiotic-Loaded Smart Platelet: A Highly Effective Invisible Mode of Killing Both Antibiotic-Sensitive and -Resistant Bacteria

“… 11 , 12 Poly(ε-caprolactone) (PCL)-based nanoparticles have been used to enhance bioavailability and encapsulate poorly water-soluble drugs against cancer, 13 − 16 infectious diseases such as malaria, 17 − 19 leishmaniasis, 20 − 22 etc., as well as chronic conditions like hypertension 23 , 24 and diabetes. 25 , 26 Poly(ε-caprolactone)-based nanoparticles have also been used for the delivery of antibiotics via different routes of administration targeting a range of bacterial infections. 27 − 30 …”

“…Additionally, several drug carriers have been developed for treating pathogens, including antibiotics loaded into liposomes and other lipid formulations, microspheres, polymeric carriers, dendrimers, and nanoplexes. − With significant advancements in novel drug delivery systems, nanomedicine has emerged as a promising strategy to achieve enhanced bioavailability and improved therapeutic efficacy while minimizing adverse effects associated with higher doses of potent drugs . Of all of the nanocarriers, biocompatible polymer and lipid-based nanoparticles, in particular, have been extensively researched for delivery of hydrophobic as well water-soluble compounds. , Polymer nanoparticles are synthesized using FDA-approved biodegradable polymers such as poly­(ε-caprolactone) (PCL), poly­(ethylene glycol) (PEG), poly­(lactic- co -glycolic acid) (PLGA), chitosan, and albumin. , Poly­(ε-caprolactone) (PCL)-based nanoparticles have been used to enhance bioavailability and encapsulate poorly water-soluble drugs against cancer, − infectious diseases such as malaria, − leishmaniasis, − etc., as well as chronic conditions like hypertension , and diabetes. , Poly­(ε-caprolactone)-based nanoparticles have also been used for the delivery of antibiotics via different routes of administration targeting a range of bacterial infections. − …”

“…11,12 Poly(ε-caprolactone) (PCL)-based nanoparticles have been used to enhance bioavailability and encapsulate poorly water-soluble drugs against cancer, 13−16 infectious diseases such as malaria, 17−19 leishmaniasis, 20−22 etc., as well as chronic conditions like hypertension 23,24 and diabetes. 25,26 Poly(ε-caprolactone)-based nanoparticles have also been used for the delivery of antibiotics via different routes of administration targeting a range of bacterial infections. 27−30 However, the clinical success of nanomedicine has been limited due to major challenges associated with existing delivery systems such as rapid clearance, lack of site-specificity, phagocytic clearance, inability to cross the blood−brain barrier, in vivo degradation, etc.…”