In-Vivo assessment of glucocorticoid loaded tea tree oil nanoemulsion gel
Optimized formulations were subjected to various in vivo studies like anti-inflammatory activity, Nickel induced dermatitis, irritation study and Acute and repeated dose dermal toxicity studies. Clobetasol propionate (CP) has anti-inflammatory, immunomodulatory, and antiproliferative activity. The aim of the present work was to test the hypothesis that the addition CP in nanoemulsions would result in enhancement CP delivery and leading to better antipsoriatic activity. Nanoemulsions were prepared by aqueous phase titration method, using Tea Tree oil, Tween 20, Transcutol P, and distilled water as the oil phase, surfactant, co-surfactant and aqueous phase, respectively.We developed a topical O/W nanoemulsion in which drug is incorporated in disperse phase of oil and evaluated its efficacy against different types of in vivostudies. It was also found that the significantly increased their anti-inflammatory activity. It was reported that CP-loaded nanoemulsion significantly increased NTPDase (Nucleoside triphosphate diphosphohydrolases) activity in lymphocytes. This membrane protein is responsible for the hydrolysis of extracellular ATP (Adenosine triphosphate) which is responsible for cell proliferation, differentiation and inflammatory processes. In vivoirritation studies did not show any irritation in spite of having high amount of surfactant. Group treated with CP loaded nanoemulsion gel showed no evident toxicity even on repeated exposure. On the basis of above in vivo study we conclude that developed nanoemulsion is safe for human.
Keywords: Clobetasol propionate, In-vivo study, Nanoemulsion, Anti-inflammatory study, Toxicity study
2. Hengge UR, Ruzicka T, Schwartz RA, Cork MJ.Adverse effects of topical glucocorticosteroids. J Am AcadDerm 2006; 54:1-15.
3. Baboota S, Alam MS, Sharma S, Kaur SJ, Anil K, Ali J. Nanocarrier-based hydrogel of betamethasone dipropionate and salicylic acid for treatment of psoriasis. Int J PharmaInvestig 2011; 1:139-147.
4. Marchiori ML, Lubini G, Nora GD, et al. Hydrogel containing dexamethasone-loaded nanocapsules for cutaneous administration: preparation, characterization and in vitro drug release study. Drug DevInd Pharm 2010; 36:962-971.
5. Christophe H, Ingo A.A.N, Yogeshvar N, Ois-Xavier M, Richard HG. Expert Review: In Vivo Methods for the Assessment of Topical Drug Bioavailability, Online published 2007.
6. Alam MS, Baboota S, Ali MS, et al. Accelerated stability testing of betamethasone dipropionate nanoemulsion. Int J Pharm PharmSci 2007; 4(4):371-374.
7. Kotta S, Khan AW, Pramod K, Ansari SH, Sharma RK, Ali J. Exploring oral nanoemulsions for bioavailability enhancement of poorly water-soluble drugs. Expert Opin Drug Deli 2012; 9(5):585-598.
8. Gordon ML. The role of clobetasol propionate emollient 0.05% in the treatment of patients with dry, scaly, corticosteroidresponsivedermatoses.ClinTher 1998; 20(1):26-39.
9. Parveen R, Baboota S, Ali J, Ahuja A, Vasudev SS, Ahmad S. Oil based nanocarrier for improved oral delivery of silymarin: in vitro and in vivo studies. Int J Pharm 2011; 413(1-2):245-253.
10. Shakeel F, Ramadan W, Gargum HM, Singh R. Preparation and in vivo evaluation of indomethacin loaded true nanoemulsions. Sci Pharm 2009; 78:47-56.
11. Senyigit T, Sonvico F, Barbieri S, Ozer O, SantiPCLecithin/chitosan nanoparticles of clobetasol-17-propionate capable of accumulation in pig skin. J Control Release 2010; 142:368- 373.
12. Di VirgilioF, Chiozzi P, Ferrari D, et al. Characterization of NTPDase (NTPDase 1; ecto-apyrase; ectodiphosphohydrolase; CD39; EC 22.214.171.124) activity in human lymphocytes. Blood 2001; 97:587- 600.
13. Burnstock G, Knight GE. Cellular distribution and functions of P2 receptor subtypes in different systems.Int Rev Cytol 2004; 240:301-304.
14. Ralevic V, Burnstock G. Involvement of purinergic signaling in cardiovascular diseases. Drug News Perspect 2003; 16:133-140.
15. Fontana MC, Rezer JFP, Coradini K, Leal DBR, Beck RCR. Improved efficacy in the treatment of contact dermatitis in rats by a dermatological nanomedicine containing clobetasol propionate. Eur J Pharm Biopharm 2011; 79:241-249.
16. Seidenari S, Di Nardo A, Giannetti A. Assessment of topical corticosteroid activity on experimentally induced contact dermatitis: echographic evaluation with binary transformation and image analysis. Skin Pharmacol 1993; 6(2):85-91.
17. Bradford MMA. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding.Anal Biochem 1976; 72:248-254.
18. Koo HJ, Lim KH, Jung HJ, Park EH. Anti-inflammatory evaluation of gardenia extract, geniposide and genipin.J Ethnopharmacol 2006; 103(3):496-500.
19. Bhadoriya SS, Mishra V, Raut S, Ganeshpurkar A, Jain SK. Anti-inflammatory and antinociceptive activities of a hydroethanolic extract of Tamarindusindica leaves. Sci Pharm 2012; 80(3): 685- 700.
20. Van-Abbe NJ, Nicholas P, Boon E. Exaggerated exposure in topical irritancy and sensitization testing. J SocCosmetChem 1975; 26:173-187.
21.Zulfakar H, Abdelouahab N, Heard CM. Enhanced topical delivery and ex vivo anti-inflammatory activity from a betamethasone dipropionate formulation containing fish oil. Inflamm Res 2010; 59:23-30.
22. Bernardi DS, Pereira TA, Maciel NR, Bortoloto J, VieraG,Oliveira GC, Rocha-Filho PA. Formation and stability of oil-in-water nanoemulsions containing rice bran oil: in vitro and in vivo assessments. J Nanobiotechnology 2011; 9:9-44.
23. Ali J, Akhtar N, Sultana Y, Baboota S, Ahuja. Antipsoriaticmicroemulsion gel formulations for topical drug delivery of babchi oil (Psoraleacorylifolia). Exp. Clin. Pharmacol 2008; 30: 277-285.
24. Pazyar N, Yaghoobi R. Suppression of Inflammatory Reactions by Terpinen-4-ol, a Main Constituent of Tea Tree Oil, in a Murine Model of Oral Candidiasis and Its Suppressive Activity to Cytokine Production of Macrophages in Vitro. The Pharmaceutical Society of Japan Biol. Pharm. Bull 2013; 36(5):838–844.
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