Chandrasekhar R B, Krishnaveni B, Krishna Mohan G, Jithan AV
Chandrasekhar R B1*, Krishnaveni B2, Krishna Mohan G3, Jithan AV4
1Department of Pharmaceutics, Vaagdevi Pharmacy College, Warangal, Telangana, India.
2Department of Pharmacognosy, Vaagdevi College of Pharmacy, Warangal, Telangana, India.
3Department of Pharmaceutical Sciences, JNTU, Hyderabad, Telangana, India.
4Department of Pharmaceutics, Omega College of Pharmacy, Hyderabad, Telangana, India.
Volume - 13,
Issue - 12,
Year - 2020
Background: The purpose of this study was to formulate nanoparticles containing Dexamethasone and to investigate their potential in the prevention of carbon tetrachloride induced liver toxicity. Methods: Dexamethasone nanoparticles were formulated using o/w emulsion solvent evaporation technique using poly-e-caprolactone as polymer. Four different nanoparticle formulations (DXMNP1, DXMNP2, DXMNP3 and DXMNP4) were prepared by taking different drug to polymer ratios. The prepared particles were characterized for particle size, drug content, PDI, surface charge potential and in-vitro drug release. The pharmacokinetics and pharmacodynamics of the Dexamethasone formulations were evaluated in male Wistar rats following iv administration, using Dexamethasone solution as reference. The pharmacokinetic parameters in rats were calculated and compared by statistical analysis. Serum glutamic pyruvic transaminase (SGPT) and Serum glutamic oxaloacetic transaminase (SGOT) were elevated. Results: The DXM nanoparticles were successfully prepared using double emulsion solvent evaporation technique. The nanoparticle formulations effectively sustained the release of the drug for more than 10 days both in vitro and in vivo. They also offered better pharmacokinetic properties to the drug than that afforded by the free drug itself. Intravenous nanoparticular administration reversed serum liver enzyme levels by 92%, compared to 60% for repeated iv administration of the solution form. Conclusion: DXM Nanoparticles showed better pharmacokinetic properties and had better prevention of liver toxicity when compared with solution.
Cite this article:
Chandrasekhar R B, Krishnaveni B, Krishna Mohan G, Jithan AV. Preparation, Characterization and In Vivo Evaluation of Dexamethasone Nanoparticles for the treatment of Liver Fibrosis. Research J. Pharm. and Tech. 2020; 13(12):6098-6104. doi: 10.5958/0974-360X.2020.01063.X
1. Luster MI, Simeonova PP, Gallucci RM, Bruccoleri A, Blazka ME, Yucesoy B. Role of inflammation in chemical-induced hepatotoxicity. Toxicol Lett. 2001; 120: 317-25.
2. Victor M, Eric OLiver. Pediatrics. 2004; 113: 1097-1106.
3. Rakesh N Pillai, Beny Baby, AJM Christina, Abin Abraham. Anti fibrotic effect of ethanolic extract of Cyclea peltata (H.F and T) roots, on carbon tetrachloride induced liver fibrosis. Research J. Pharm. and Tech. 2009; 2(1):201-205.
4. Sahil Choudhari, Jothipriya A. Non-Alcoholic Fatty Liver Disease. Research J. Pharm. and Tech. 2016; 9(10):1782-1785.
5. Bataller R, Brenner DA. Hepatic stellate cells as a target for the treatment of liver fibrosis. Semin Liver Dis. 2001; 21:437-51.
6. Ikeda K, Lin C, Olaso E., et al. Discoidin domain receptor 2 (DDR2) interacts with SRC and SHC following activation by collagen I. Hepatology. 2000; 32:315.
7. Ki SH, Choi DW, Kim CW, Kim SG. Lack of therapeutic improvement of liver fibrosis in rats by dexamethasone in spite of ascites amelioration. Chemico-biological interactions. 2005 Feb 28; 152(1):37-47.
8. Karnakumar V Biradar, Chandrashekhar B Patil, Basavaraj V Chivde, MH Malipatil, Sanjivkumar D Biradar. Effect of Superoxide Dismutase Mimetic Tempol on Dexamethasone Induced Insulin Resistance-Role of Oxidative Stress. Research J. Pharmacology and Pharmacodynamics. 2011; 3(3): 134-137.
9. Melgert BN, Olinga P, Jack VK, Molema G, Meijer DK, Poelstra K. Dexamethasone coupled to albumin is selectively taken up by rat nonparenchymal liver cells and attenuates LPS-induced activation of hepatic cells. Journal of hepatology. 2000 Apr 1; 32(4):603-11.
10. Utpal Jana, Sovan Pal, G.P. Mohanta, P.K. Manna, R. Manavalan. Nanoparticles: A Potential Approach for Drug Delivery. Research J. Pharm. and Tech. 2011; 4(7):1016-1019.
11. Ch. Prabhakar, K. Bala Krishna. A Review on Polymeric Nanoparticles. Research J. Pharm. and Tech. 2011; 4(4): 496-498.
12. Sium-Ul Hossain Miah, Mehedi Faysal, Asraful Islam, Nusrat Jahan, Bibekananda Saha, Md. Mazharul Karim, Mohiuddin Ahmed Bhuiyan. Fabrication and In-Vitro Evaluation of Sustained Release Aceclofenac Microspheres by Emulsion Solvent Evaporation Technique. Research J. Pharm. and Tech.2013; 6(7):765-768.
13. Rout Prasant Kumar, Ghosh Amitava, Nayak Udaya Kumar, Nayak Bhabani Shankar. Formulation Design, Preparation of Losartan Potassium Microspheres by W/O Emulsion Solvent Evaporation Method and It’s in Vitro Characterization. Research J. Pharm. and Tech.2009; 2 (3):513-516.
14. Anuradha CA, Aukunuru J. Preparation, characterization and in vivo evaluation of Bis-demethoxy curcumin analogue (BDMCA) nanoparticles. Trop J Pharm Res. 2010; 9: 51-58.
15. CPCSEA guidelines for laboratory animal facility. Indian J Pharmacol. 2003; 35: 257- 274.
16. Demers G, Griffin G, De Vroey G, Haywood JR, Zurlo J, Bedard M. Harmonization of Animal Care and Use Guidance. Science 2006; 312: 700-701.
17. Yun-Kyoung Song, Jeong-Sook Park, Jin-Ki Kim, and Chong-Kook Kim. HPLC Determination of Dexamethasone in Human Plasma. Journal of liquid chromatography and related technologies. 2004; 27(14):2293-2306.
18. Rakesh N Pillai, Beny Baby, AJM Christina, Abin Abraham. Anti fibrotic effect of ethanolic extract of Cyclea peltata (H.F and T) roots, on carbon tetrachloride induced liver fibrosis. Research J. Pharm. and Tech. 2009; 2(1):201-205.
19. Konatham S, Nyathani H, Bonepally CR, Yeannameneni P, Aukunuru J. Liposomal delivery of curcumin to liver. Turk J Pharm Sci. 2010; 7: 89-98.
20. Ashok Reddy B, Satish S, Sankara G, Adithya Sarma, Sai Kishore V. Influence of Solvents on Entrapment Efficiency and Drug Release rate of Propranolol Hydrochloride from Ethyl Cellulose Microcapsules. Asian J. Research Chem.2011;4(1):143-146.
21. Archana A, Manikanta Kumar A, Manjunath Shetty KS. Formulation Development and Evaluation of Sumatryptan Pulsatile Drug Delivery using Pulsincap Technology. Research J. Pharm. and Tech.2013; 6(12):1375-1379.