STUDY OF ENHANCED ANTI-INFLAMMATORY POTENTIAL OF NIGELLA SATIVA IN TOPICAL NANOFORMULATION
DOI:
https://doi.org/10.22159/ijpps.2018v10i7.22966Keywords:
Thymoquinone, Pseudo-ternary phase diagram, Stress stability, Nanoemulsion, Anti-inflammatory, FluxAbstract
Objective: Formulate a nanocarrier for enhancing the anti-inflammatory activity of thymoquinone (Tq), a major active constituent of Nigella sativa.
Methods: Nanoformulation of Tq was developed by low energy emulsification techniques. NanoTqs were pre-screened by different thermodynamic stability tests, followed by in vitro release, zeta potential, viscosity, the transmittance (%), globule size distribution and ex vivo studies. The morphology of the optimized NanoTq was determined by transmission electron microscopy (TEM) which revealed fairly spherical shape and good correlation with particle size distribution study. The formulation used for assessment of the anti-inflammatory potential and permeability enhancement contained mixture of essential oil of Nigella sativa: Capryol 90 (3:7, 10%, v/v), Tween 80 (21.75%, v/v), PEG 400 (7.25%, v/v) and double distilled water (61%, v/v).
Results: The in vitro permeation of Tq from optimized formulations was found extremely significant (p<0.001) in comparison to apiTq. The steady state flux (Jss), the permeability coefficient (Kp) and enhancement ratio (Er) of NanoTq gel was determined and compared with apiTq. The comparative anti-inflammatory effects of the optimized formulations NanoTq, apiTq and DicloGel was assessed on the edema in the carrageenan-induced paw model in Wistar rats. Therapeutic potential of NanoTq was found statistically extremely significant (P<0.0001) compared to apiTq and insignificant comparable with standard DicloGel. Storage stability of NanoTq showed insignificant changes in the zeta potential, droplet size and was free from any physical instability.
Conclusion: The optimized nano formulation with a lower dose of Tq showed better anti-inflammatory effects, indicating greater absorption capability through the stratum corneum.
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References
Sharrif MM. Nigella sativa traditional usages (Black Seed). Adv Environ Biol 2011;5:5-16.
ALâ€Naqeeb G, Ismail M. Regulation of apolipoprotein A-1 and apolipoprotein B100 genes by thymoquinone rich fraction and thymoquinone in hepg2 cells. J Food Lipids 2009;16:245-58.
Mariod AA, Ibrahim RM, Ismail M, Ismail N. Antioxidant activity and phenolic content of phenolic-rich fractions obtained from black cumin (nigella sativa) seedcake. Food Chem 2009;116:306-12.
Houghton PJ, Zarka R, de Las Heras B, Hoult JR. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Med 1995;61:33-6.
Nagi MN, Alam K, Badary OA, Al-Shabanah OA, Al-Sawaf HA, Al-Bekairi AM. Thymoquinone protects against carbon tetracholide hepatotoxicity in mice via an antioxidant mechanism. Biochem Mol Biol Int 1999;47:153-9.
Burits M, Bucar F. Antioxidant activity of nigella sativa essential oil. Phytother Res 2000;14:323-8.
Kumara SS, Huat BT. Extraction, isolation and characterization of anti-tumour principle, alpha-hedrin, from the seeds of nigella sativa. Planta Med 2001;67:29-32.
Sedaghat R, Roghani M, Khalili M. Neuroprotective effect of thymoquinone, the nigella sativa bioactive compound, in a 6-hydroxydopamine-induced hemi-parkinsonian rat model. Iran J Pharm Res 2014;13:227-34.
Ismail N, Ismail M, Mazlan M, Latiff LA, Imam MU, Iqbal S, et al. Thymoquinone prevents β-amyloid neurotoxicity in primary cultured cerebellar granule neurons. Cell Mol Neurobiol 2013;33:1159-69.
Akhtar M, Maikiyo AM, Najmi AK, Khanam R, Mujeeb M, Aqil M. Neuroprotective effects of chloroform and petroleum ether extracts of nigella sativa seeds in stroke model of rat. J Pharm Bioallied Sci 2013;5:119-25.
El-Gazzar M, El-Mezayen R, Marecki JC, Nicolls MR, Canastar A, Dreskin SC. Anti-inflammatory effect of thymoquinone in a mouse model of allergic lung inflammation. Int Immunopharmacol 2006;6:1135-42.
Mansour MA, Tornhamre S. Thymoquinone inhibits 5-lipoxygenase and leukotriene C4 synthase in human blood cell. J Enzym Inhib Med Chem 2004;19:431-6.
Al-Ghamdi M. Anti-inflammatory, analgesic and antipyretic activity of nigella sativa. J Ethnopharmacol 2001;76:45-8.
Odeh F, Ismail SI, Abu-Dahab R, Mahmoud IS, Al-Bawab A. Thymoquinone in liposomes: a study of loading efficiency and biological activity towards breast cancer. Drug Delivery 2012;19:371-7.
Dhawan B, Aggarwal G, Harikumar S. Enhanced transdermal permeability of piroxicam through novel nanoemulgel formulation. Int J Pharm Investig 2014;4:65-76.
Shakeel F, Ramadan W, Ahmed MA. Investigation of true nanoemulsions for the transdermal potential of indomethacin: characterization, rheological characteristics, and ex vivo skin permeation studies. J Drug Target 2009;7:435-41.
Shakeel F, Ramadan W, Rizwan M, Faiyazuddin M, Mustafa G, Shafiq S, et al. Transdermal and topical delivery of anti-inflammatory agents using nanoemulsion/microemulsion: an updated review. Curr Nano Sci 2010;6:184-98.
Ahad A, Aqil M, Kohli K, Chaudhary H, Sultana Y, Mujeeb M, et al. Chemical penetration enhancers: a patent review. Expert Opin Ther Pat 2009;19:969-88.
Talegaonkar S, Mustafa G, Akhter S, Iqbal ZI. Design and development of oral oil-in-water nanoemulsion formulation bearing atorvastatin: in vitro assessment. J Dispersion Sci Technol 2009;30:1-12.
Liu Y, Yu XM, Sun RJ, Pan XL. Folate-functionalized lipid nanoemulsion to deliver chemo-radiotherapeutics together for the effective treatment of nasopharyngeal carcinoma. AAPS PharmSciTech 2017;18:1374-81.
Afzal SM, Shareef MZ, Dinesh T, Kishan V. Folate-PEG-decorated docetaxel lipid nanoemulsion for improved antitumor activity. Nanomedicine 2016;11:2171-84.
Constantinides PP. Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm Res 1995;12:1561-72.
Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Delivery Rev 2000;45:89:121.
Faiyazuddin M, Akhtar N, Akhter J, Shakeel F, Shafiq S, Mustafa G, et al. Production, characterization, in vitro and ex vivo studies of babchi oil-encapsulated nanostructured solid lipid carriers produced by a hot aqueous titration method. Pharmazie 2010;65:347-54.
Ghosheh OA, Houdi AA, Crooks PA. High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). J Pharm Biomed Anal 1999;19:757-62.
Faiyazuddin M, Akhtar J, Mustafa G. Formulation of tea tree essential oil-loaded nanoemulsion system using aqueous titration method: In vitro and ex vivo kinetics. Int J Essential Oil Ther 2009;3:22-7.
Mustafa G, Khan ZI, Bansal T, Talegaonkar S. Preparation and characterization of oil in water nano-reservoir systems for improved oral delivery of atorvastatin. Curr Nano Sci 2009;5:428-40.
Mustafa G, Baboota S, Ahuja A, Ali J. Formulation development of chitosan-coated intra nasal ropinirole nanoemulsion for better management option of parkinson: an in vitro ex vivo evaluation. Curr Nano Sci 2012;8:348-60.
Mikolaj M, Yerramreddy TR, Ghosh P, Crooks PA, Stinchcomba AL. In vitro permeation of a pegylated naltrexone prodrug across the microneedle-treated skin. J Controlled Release 2010;146:37-44.
Anwer MK, Jamil S, Ibnouf EO, Shakeel F. Enhanced antibacterial effects of clove essential oil by nanoemulsion. J Oleo Sci 2014;63:347-54.
Wintr CA, Risley EA, Nuss GW. Carrageenin-induced edema in hind paws of the rat as an assay for anti-inflammatory drugs. Proc Soc Exp Biol Med 1962;111:544-7.
Ghosh MN. Fundamentals of experimental Pharmacology. 3rd edition. Hilton and Company, Kolkata, India; 2005. p. 192-3.
Rao J, McClements DJ. Formation of flavor oil micro-emulsions, nanoemulsions and emulsions: influence of composition and preparation method. J Agric Food Chem 2011;59:5026-35.
Craig DQM, Barker SA, Banning D. An investigation into the mechanisms of self-emulsification using particle size analysis and low-frequency dielectric spectroscopy. Int J Pharm 1995;114:103-10.
Boucher EA. Separation of small-particle dispersions by the preferential accumulation in one of two liquid phases, or by static flotation at their interface. J Chem Soc Faraday Trans 1989;85:2963-72.
Bhardwaj A, Hartland S. Dynamics of emulsification and demulsification of water in crude oil emulsions. Ind Eng Chem Res 1994;33:1271-9.
Schleich N, Preat V. Nanostructures overcoming the skin barriers: Drug delivery strategy: In ch 6.2 by Alonso MJ, Csaba NS. Nanostructure biomaterials for overcoming biolologicas barriers: The Royal Society of Chemistry, UK; 2012.
Tan G, Xu P, Lawson LB, He J, Freytag LC, Clements JD, et al. Hydration effects on skin microstructure as probed by high-resolution cryo-scanning electron microscopy and mechanistic implications to enhanced transcutaneous delivery of biomacromolecules. J Pharm Sci 2010;99:730-40.
Finlay TM, Abdulkhalek S, Gilmour A, Guzzo C, Jayanth P, Amith SR, et al. Thymoquinone-induced Neu4 sialidase activates NFκB in macrophage cells and pro-inflammatory cytokines in vivo. Glycoconj J 2010;27:583-600.
Wang Y, Gao H, Zhang W, Zhang W, Fang L. Thymoquinone inhibits lipopolysaccharide-induced inflammatory mediators in BV2 microglial cells. Int Immunopharmacol 2015;26:169-73.
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