DDA LOADED PCL NANOPARTICLES ENHANCES THE ORAL BIOAVAILABILITY OF DDA IN DIABETES INDUCED EXPERIMENTAL RATS


Nagalakshmi Kamaraj, Sujatha S, Alwin D

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 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 (105.6±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.


Keywords


DDA, Nano-DDA, Nanoencapsulation, Oral bioavailability, Antidiabetic, Drug release, HPLC

| PDF | HTML |

References


Ooi JP, Kuroyanagi M, Sulaiman SF, Muhammad TST, Tan ML. Andrographolide and 14-deoxy-11, 12-didehydro-andro-grapholide inhibit cytochrome P450s in HepG2 hepatoma cells. Life Sci 2011;88:216-23.

Sattayasai J, Srisuwan S, Arkaravichien T, Aromdee C. Effects of andrographolide on sexual functions, vascular reactivity and serum testosterone level in rodents. Food Chem Toxicol 2010;48:1934-8.

Pholphana N, Rangkadilok N, Saehun J, Ritruechai S, Satayavivad J. Changes in the contents of four active diterpenoids at different growth stages in Andrographis paniculata (Burm. f.) Nees (Chuanxinlian). Chin Med 2013;8:1749-6.

Yoopan N, Thisoda P, Rangkadilok N, Sahasitiwat S, Pholphana N, Ruchirawat S, et al. Cardiovascular effects of 14-deoxy-11,12-didehydroandrographolide and Andrographis paniculata extracts. Planta Med 2007;73:503–11.

Wu TS, Chern HJ, Damu AG, Kuo PC, Su CR, Lee EJ, et al. Flavonoids and ent-labdane diterpenoids from Andrographis paniculata and their antiplatelet aggregatory and vasorelaxing effects. J Asian Nat Prod Res 2008;10:17–24.

Lee MJ, Rao YK, Chen K, Lee YC, Chung YS, Tzeng YM. Andrographolide and 14-deoxy-11,12-didehydroandro-grapholide from Andrographis paniculata attenuate high glucose-induced fibrosis and apoptosis in murine renal mesangeal cell lines. J Ethnopharmacol 2010;132:497-505.

Panossian AG. Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human. Phytomedicine 2000;7:351-64.

Pholphana N, Panomvana D, Rangkadilok N, Suriyo T, Puranajoti P, Ungtrakul T, et al. Andrographis paniculata: dissolution investigation and pharmacokinetic studies of four major active diterpenoids after multiple oral dose administration in healthy thai volunteers. J Ethnopharmacol 2016;194:513-21.

Zanchetta B, Chaud MV, Santana MHA. Self-emulsifying drug delivery systems (SEDDS) in pharmaceutical development. J Adv Chem Eng 2015;5:130.

Nagalakshmi K, Pooja YR, Praveenkumar I, Sujatha S. Fabrication, characterization, in vitro drug release and glucose uptake activity of 14-deoxy, 11, 12-didehydroandrographolide loaded polycaprolactone nanoparticles. Asian J Pharm Sci; 2003. Doi.10.1016/j.ajps.2017.02.003.

Szkudelski T. Streptozotocin-nicotinamide-induced diabetes in the rat. Characteristics of the experimental model. Exp Biol Med 2012;237:481–90.

Fröde TS, Medeiros YS. Animal models to test drugs with potential antidiabetic activity. J Ethnopharmacol 2008;115:173–83.

Wan S, Sun Y, Qi X, Tan F. Improved bioavailability of poorly water-soluble drug curcumin in cellulose acetate solid dispersion. AAPS PharmSciTech 2012;13:159–66.

Isadiatruti D, T Budiati, S Martodihardjo. Bioavailability study of a physical mixture of carbamazepine and amino acids. Asian J Pharm Clin Res 2015;8:592-5.

Shin SC, Choi JS, Li X. Enhanced bioavailability of tamoxifen after oral administration of tamoxifen with quercetin in rats. Int J Pharm 2006;313:144–9.

Chawla JS, Amiji MM. Biodegradable poly(epsilon-caprolactone) nanoparticles for tumor-targeted delivery of tamoxifen. Int J Pharm 2002;249:127–38.

Kamil A, Chen CYO, Blumberg JB. Nanotechnology and functional foods: effective delivery of bioactive ingredients. John Wiley and Sons, Ltd, Chichester, UK. 2015:158–74.

Sun H, Mei L, Song C, Cui X, Wang P. The in vivo degradation, absorption and excretion of the PCL-based implant. Biomaterials 2006;27:1735–40.

Dhana Lekshmi UM, Poovi G, Neelakanta Reddy P. In vitro observation of repaglinide engineered polymeric nanoparticles. Dig J Nanomater Biostructures 2012;7:1-18.

Gao Y, Li Z, Sun M, Li H, Guo C, Cui J, et al. Preparation, characterization, pharmacokinetics, and tissue distribution of curcumin nanosuspension with TPGS as a stabilizer. Drug Dev Ind Pharm 2010;36:1225–34.

Xie X, Tao Q, Zou Y, Zhang F, Guo M, Wang Y, et al. PLGA nanoparticles improve the oral bioavailability of curcumin in rats: characterizations and mechanisms, J Agric Food Chem 2011;59:9280–9.

Chang KL, Tan B, Chang KL, Lim BK, Chiu GN. Perorally active nano micellar formulation of quercetin in the treatment of lung cancer perorally active nano-micellar formulation of quercetin in the treatment of lung cancer. Int J Nanomed 2012;7:651–61.

Yao Y, Liao QF, Xie ZY, Zeng YE, Ma Y. Absorption mechanism of dihydro andrographolide in human Caco-2 cell monolayer model. Chinese Tradit Herb Drugs 2011;42:1154-57.

Ye L, T Wang, L Tang, W Liu, Z Yang, J Zhou, et al. Poor oral bioavailability of a promising anticancer agent andro-grapholide is due to extensive metabolism and efflux by P‐glycoprotein. J PharmSci 2011;100:5007–17.




About this article

Title

DDA LOADED PCL NANOPARTICLES ENHANCES THE ORAL BIOAVAILABILITY OF DDA IN DIABETES INDUCED EXPERIMENTAL RATS

Keywords

DDA, Nano-DDA, Nanoencapsulation, Oral bioavailability, Antidiabetic, Drug release, HPLC

DOI

10.22159/ijpps.2017v9i4.16860

Date

03-03-2017

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 9, Issue 4, 2017 Page: 198-202

Online ISSN

0975-1491

Statistics

40 Views | 20 Downloads

Authors & Affiliations

Nagalakshmi Kamaraj
Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur-603203
India

Sujatha S
Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur-603203
India

Alwin D
Central Animal House, SRM MCH & Research Center, SRM University, Kattankulathur-603203
Lao People's Democratic Republic


Article Tools


Share

Refbacks

  • There are currently no refbacks.