Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Nigella sativa Oil-loaded Ethanolic Vesicular Gel for Imiquimod-induced Plaque Psoriasis: Physicochemical Characterization, Rheological Studies, and In vivo Efficacy

Author(s): Samar Vihal, Swati Pundir, Charul Rathore, Uma Ranjan Lal, Gaurav Gupta, Sachin Kumar Singh, Kamal Dua, Dinesh Kumar Chellappan* and Poonam Negi*

Volume 22, Issue 1, 2025

Published on: 02 July, 2024

Page: [80 - 91] Pages: 12

DOI: 10.2174/0115672018246645231019131748

Price: $65

Open Access Journals Promotions 2
Abstract

Background: The therapeutic effect of NS oil in mild to moderate psoriasis is limited owing to low play load of thymoquinone (<15 %w/w), irritation, dripping, low viscosity and thus, less contact time on the lesions.

Aims: This study aimed at developing and characterizing the ethanolic vesicular hydrogel system of Nigella sativa (NS) oil (NS EV hydrogel) for the enhancement of anti-psoriatic activity.

Objective: The objective of this study was to develop NS EV hydrogel and evaluate its anti-psoriatic activity.

Methods: The identification and quantification of TQ content in different NS seed extracts and marketed oil were measured by an HPTLC method using n-hexane and ethyl acetate as solvent systems. Preparation of ethanolic vesicles (EVs) was performed by solvent injection method, while its antipsoriatic activity was evaluated employing an Imiquad (IMQ)-induced plaque psoriasis animal model.

Results: A compact HPTLC band was obtained for TQ at an Rf value of 0.651. The calibration plot was linear in the range of 1-10 μg/spot, and the correlation coefficient of 0.990 was indicative of good linear dependence of peak area on concentration. From the different NS sources, the high TQ content was obtained in the marketed cold press oil, i.e., 1.45±0.08 mg/ml. Out of various NS oilloaded EVs, the F6 formulation revealed the smallest particle size (278.1 nm), with log-normal size distribution (0.459) and adequate entrapment efficiency. A non-uniform shape was observed in the transmission electron microscopy. The viscosity of F6 formulation hydrogel was 32.34 (Pa·s), which exhibited plastic behavior. In vivo, efficacy studies demonstrated decreased inflammation of the epidermis and dermis and a marked decrease in the levels of IL-17 by NS EV hydrogel compared to plain NS oil and standard drugs (Betamethasone and Dr. JRK Psorolin Oil).

Conclusion: It may be concluded from the findings that NS-loaded EV gel was as good as betamethasone cream but more efficacious than the other treatments.

Keywords: Nigella sativa, psoriasis, imiquad, ethanolic vesicles, thymoquinone, micromeritics.

« Previous
Graphical Abstract
[1]
Ramadan, M.F. Nutritional value, functional properties and nutraceutical applications of black cumin (Nigella sativa L.): An overview. Int. J. Food Sci. Technol., 2007, 42(10), 1208-1218.
[http://dx.doi.org/10.1111/j.1365-2621.2006.01417.x]
[2]
Eid, A.M. A review on the cosmeceutical and external applications of Nigella sativa. J. Trop. Med., 2017, 2017, 7092514.
[3]
Yaman, İ.; Balikci, E. Protective effects of nigella sativa against gentamicin-induced nephrotoxicity in rats. Exp. Toxicol. Pathol., 2010, 62(2), 183-190.
[http://dx.doi.org/10.1016/j.etp.2009.03.006] [PMID: 19398313]
[4]
Ali, B.; Blunden, G. Pharmacological and toxicological properties of Nigella sativa. Phytother. Res., 2003, 17(4), 299-305.
[http://dx.doi.org/10.1002/ptr.1309]
[5]
Chandrasekar, R.; Sivagami, B. Alternative treatment for psoriasis-A review. Int. J. Res. Dev. Pharm. Life Sci., 2016, 5(4), 2188-2197.
[6]
Thakur, S.; Kaurav, H.; Chaudhary, G. Nigella sativa (Kalonji): A black seed of miracle. Int. J. Res. Rev., 2021, 8(4), 342-357.
[http://dx.doi.org/10.52403/ijrr.20210441]
[7]
Michalek, I.M.; Loring, B.; John, S.M. A systematic review of worldwide epidemiology of psoriasis. J. Eur. Acad. Dermatol. Venereol., 2017, 31(2), 205-212.
[http://dx.doi.org/10.1111/jdv.13854] [PMID: 27573025]
[8]
Sun, L.; Liu, Z.; Lin, Z.; Cun, D.; Tong, H.; Yan, R.; Wang, R.; Zheng, Y. Comparison of normal versus imiquimod-induced psoriatic skin in mice for penetration of drugs and nanoparticles. Int. J. Nanomedicine, 2018, 13, 5625-5635.
[http://dx.doi.org/10.2147/IJN.S170832] [PMID: 30271151]
[9]
Mascarenhas-Melo, F.; Carvalho, A.; Gonçalves, M.B.S.; Paiva-Santos, A.C.; Veiga, F. Nanocarriers for the topical treatment of psoriasis - pathophysiology, conventional treatments, nanotechnology, regulatory and toxicology. Eur. J. Pharm. Biopharm., 2022, 176, 95-107.
[http://dx.doi.org/10.1016/j.ejpb.2022.05.012] [PMID: 35605927]
[10]
Pradhan, M.; Alexander, A.; Singh, M.R.; Singh, D.; Saraf, S.; Saraf, S. Ajazuddin, Understanding the prospective of nano-formulations towards the treatment of psoriasis. Biomed. Pharmacother., 2018, 107, 447-463.
[http://dx.doi.org/10.1016/j.biopha.2018.07.156] [PMID: 30103117]
[11]
Martin, G.; Young, M.; Aldredge, L. Recommendations for initiating systemic therapy in patients with psoriasis. J. Clin. Aesthet. Dermatol., 2019, 12(4), 13-26.
[PMID: 31119006]
[12]
Jain, A.; Doppalapudi, S.; Domb, A.J.; Khan, W. Tacrolimus and curcumin co-loaded liposphere gel: Synergistic combination towards management of psoriasis. J. Control. Release, 2016, 243, 132-145.
[http://dx.doi.org/10.1016/j.jconrel.2016.10.004] [PMID: 27725194]
[13]
Dadwal, A.; Mishra, N.; Narang, R.K. Novel topical nanocarriers for treatment of psoriasis: An overview. Curr. Pharm. Des., 2019, 24(33), 3934-3950.
[http://dx.doi.org/10.2174/1381612824666181102151507] [PMID: 30387390]
[14]
Yadav, K.; Singh, D.; Singh, M.R. Novel archetype in psoriasis management bridging molecular dynamics in exploring novel therapies. Eur. J. Pharmacol., 2021, 907, 174254.
[http://dx.doi.org/10.1016/j.ejphar.2021.174254] [PMID: 34118225]
[15]
Hwang, J.R.; Cartron, A.M.; Khachemoune, A. A review of Nigella sativa plant‐based therapy in dermatology. Int. J. Dermatol., 2021, 60(12), e493-e499.
[http://dx.doi.org/10.1111/ijd.15615] [PMID: 33899217]
[16]
Okasha, E.F.; Bayomy, N.A.; Abdelaziz, E.Z. Effect of topical application of black seed oil on imiquimod‐induced psoriasis‐like lesions in the thin skin of adult male albino rats. Anat. Rec., 2018, 301(1), 166-174.
[http://dx.doi.org/10.1002/ar.23690] [PMID: 28926201]
[17]
Palaniswamy, D.; Nithyanantham, M.; Raghu, P.S.; Dwarampudi, L.P. Antipsoriatic activity and cytotoxicity of ethanolic extract of Nigella sativa seeds. Pharmacogn. Mag., 2012, 8(32), 268-272.
[http://dx.doi.org/10.4103/0973-1296.103650] [PMID: 24082629]
[18]
Ahmed Jawad, H.; Ibraheem Azhar, Y.; Al-Hamdi Khalil, I. Evaluation of efficacy, safety and antioxidant effect of Nigella sativa in patients with psoriasis: A randomized clinical trial. J Clin Exp Invest, 2014, 5(2), 186-193.
[http://dx.doi.org/10.5799/ahinjs.01.2014.02.0387]
[19]
Zheng, Y.; Zhang, Q.; Hu, X. A comprehensive review of ethnopharmacological uses, phytochemistry, biological activities, and future prospects of Nigella glandulifera. Med. Chem. Res., 2020, 29(7), 1168-1186.
[http://dx.doi.org/10.1007/s00044-020-02558-9]
[20]
Rathore, C.; Rathbone, M.J.; Chellappan, D.K.; Tambuwala, M.M.; Pinto, T.D.J.A.; Dureja, H.; Hemrajani, C.; Gupta, G.; Dua, K.; Negi, P. Nanocarriers: More than tour de force for thymoquinone. Expert Opin. Drug Deliv., 2020, 17(4), 479-494.
[http://dx.doi.org/10.1080/17425247.2020.1730808] [PMID: 32077770]
[21]
Alexander, A. Ajazuddin; Patel, R.J.; Saraf, S.; Saraf, S. Recent expansion of pharmaceutical nanotechnologies and targeting strategies in the field of phytopharmaceuticals for the delivery of herbal extracts and bioactives. J. Control. Release, 2016, 241, 110-124.
[http://dx.doi.org/10.1016/j.jconrel.2016.09.017] [PMID: 27663228]
[22]
Roshini, R.; Saraswathi, T.; Xdamodharanie, M. Ethosomes: Novel lipid vesicular and non-invasive delivery carrier–A review. J. Posit. Sch. Psychol., 2022, 6(8), 4099-4111.
[23]
Verma, P.; Pathak, K. Therapeutic and cosmeceutical potential of ethosomes: An overview. J. Adv. Pharm. Technol. Res., 2010, 1(3), 274-282.
[http://dx.doi.org/10.4103/0110-5558.72415] [PMID: 22247858]
[24]
Negi, P.; Singh, B.; Sharma, G.; Katare, O.P. Enhanced topical delivery of lidocaine via ethosomes-based hydrogel: Ex-vivo and in-vivo evaluation. J. Nanopharm. Drug Deliv., 2014, 2(2), 138-147.
[http://dx.doi.org/10.1166/jnd.2014.1054]
[25]
Kumari, S.; Goyal, A.; Sönmez Gürer, E.; Algın Yapar, E.; Garg, M.; Sood, M.; Sindhu, R.K. Bioactive loaded novel nano-formulations for targeted drug delivery and their therapeutic potential. Pharmaceutics, 2022, 14(5), 1091.
[http://dx.doi.org/10.3390/pharmaceutics14051091] [PMID: 35631677]
[26]
Negi, P.; Sharma, I.; Hemrajani, C.; Rathore, C.; Bisht, A.; Raza, K.; Katare, O.P. Thymoquinone-loaded lipid vesicles: A promising nanomedicine for psoriasis. BMC Complement. Altern. Med., 2019, 19(1), 334.
[http://dx.doi.org/10.1186/s12906-019-2675-5] [PMID: 31771651]
[27]
Alam, P.; Yusufoglu, H.; Alam, A. HPTLC densitometric method for analysis of thymoquinone in Nigella sativa extracts and marketed formulations. Asian Pac. J. Trop. Dis., 2013, 3(6), 467-471.
[http://dx.doi.org/10.1016/S2222-1808(13)60102-4]
[28]
Velho-Pereira, R.M.; Barhate, C.R.; Kulkarni, S.R.; Jagtap, A.G. Validated high-performance thin-layer chromatographic method for the quantification of thymoquinone in Nigella Sativa extracts and formulations. Phytochem. Anal., 2011, 22(4), 367-373.
[http://dx.doi.org/10.1002/pca.1289] [PMID: 21337651]
[29]
Raza, K.; Singh, B.; Lohan, S.; Sharma, G.; Negi, P.; Yachha, Y.; Katare, O.P. Nano-lipoidal carriers of tretinoin with enhanced percutaneous absorption, photostability, biocompatibility and anti-psoriatic activity. Int. J. Pharm., 2013, 456(1), 65-72.
[http://dx.doi.org/10.1016/j.ijpharm.2013.08.019] [PMID: 23973754]
[30]
Abd El-Alim, S.H.; Kassem, A.A.; Basha, M.; Salama, A. Comparative study of liposomes, ethosomes and transfersomes as carriers for enhancing the transdermal delivery of diflunisal: in vitro and in vivo evaluation. Int. J. Pharm., 2019, 563, 293-303.
[http://dx.doi.org/10.1016/j.ijpharm.2019.04.001] [PMID: 30951860]
[31]
Raza, K.; Singh, B.; Mahajan, A.; Negi, P.; Bhatia, A.; Katare, O.P. Design and evaluation of flexible membrane vesicles (FMVs) for enhanced topical delivery of capsaicin. J. Drug Target., 2011, 19(4), 293-302.
[http://dx.doi.org/10.3109/1061186X.2010.499464] [PMID: 20615093]
[32]
Negi, P.; Singh, B.; Sharma, G.; Beg, S.; Raza, K.; Katare, O.P. Phospholipid microemulsion-based hydrogel for enhanced topical delivery of lidocaine and prilocaine: QbD-based development and evaluation. Drug Deliv., 2016, 23(3), 941-957.
[http://dx.doi.org/10.3109/10717544.2014.923067] [PMID: 24892623]
[33]
Agrawal, M.; Saraf, S.; Pradhan, M.; Patel, R.J.; Singhvi, G. Ajazuddin; Alexander, A. Design and optimization of curcumin loaded nano lipid carrier system using Box-Behnken design. Biomed. Pharmacother., 2021, 141, 111919.
[http://dx.doi.org/10.1016/j.biopha.2021.111919] [PMID: 34328108]
[34]
Jain, S.; Patel, N.; Madan, P.; Lin, S. Formulation and rheological evaluation of ethosome-loaded carbopol hydrogel for transdermal application. Drug Dev. Ind. Pharm., 2016, 42(8), 1315-1324.
[http://dx.doi.org/10.3109/03639045.2015.1132227] [PMID: 26727599]
[35]
Negi, P.; Aggarwal, M.; Sharma, G.; Rathore, C.; Sharma, G.; Singh, B.; Katare, O.P. Niosome-based hydrogel of resveratrol for topical applications: An effective therapy for pain related disorder(s). Biomed. Pharmacother., 2017, 88, 480-487.
[http://dx.doi.org/10.1016/j.biopha.2017.01.083] [PMID: 28126673]
[36]
Badanthadka, M.; D’Souza, L. Imiquimod-induced psoriasis mice model: A promising tool for psoriasis research? Res J Pharm Technol, 2020, 13(7), 3508-3515.
[http://dx.doi.org/10.5958/0974-360X.2020.00621.6]
[37]
Chandra, A.; Aggarwal, G.; Manchanda, S.; Narula, A. Development of topical gel of methotrexate incorporated ethosomes and salicylic acid for the treatment of psoriasis. Pharm. Nanotechnol., 2019, 7(5), 362-374.
[http://dx.doi.org/10.2174/2211738507666190906123643] [PMID: 31490769]
[38]
Touitou, E.; Dayan, N.; Bergelson, L.; Godin, B.; Eliaz, M. Ethosomes — novel vesicular carriers for enhanced delivery: Characterization and skin penetration properties. J. Control. Release, 2000, 65(3), 403-418.
[http://dx.doi.org/10.1016/S0168-3659(99)00222-9] [PMID: 10699298]
[39]
Garg, B.J.; Garg, N.K.; Beg, S.; Singh, B.; Katare, O.P. Nanosized ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery against vitiligo: Formulation optimization, in vitro evaluation and preclinical assessment. J. Drug Target., 2016, 24(3), 233-246.
[http://dx.doi.org/10.3109/1061186X.2015.1070855] [PMID: 26267289]
[40]
van der Fits, L.; Mourits, S.; Voerman, J.S.A.; Kant, M.; Boon, L.; Laman, J.D.; Cornelissen, F.; Mus, A.M.; Florencia, E.; Prens, E.P.; Lubberts, E. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J. Immunol., 2009, 182(9), 5836-5845.
[http://dx.doi.org/10.4049/jimmunol.0802999] [PMID: 19380832]
[41]
Mostafa, M.; Alaaeldin, E.; Aly, U.F.; Sarhan, H.A. Optimization and characterization of thymoquinone-loaded liposomes with enhanced topical anti-inflammatory activity. AAPS PharmSciTech, 2018, 19(8), 3490-3500.
[http://dx.doi.org/10.1208/s12249-018-1166-1] [PMID: 30218265]
[42]
Jain, A.; Pooladanda, V.; Bulbake, U.; Doppalapudi, S.; Rafeeqi, T.A.; Godugu, C.; Khan, W. Liposphere mediated topical delivery of thymoquinone in the treatment of psoriasis. Nanomedicine, 2017, 13(7), 2251-2262.
[http://dx.doi.org/10.1016/j.nano.2017.06.009] [PMID: 28647592]
[43]
Doppalapudi, S.; Jain, A.; Chopra, D.K.; Khan, W. Psoralen loaded liposomal nanocarriers for improved skin penetration and efficacy of topical PUVA in psoriasis. Eur. J. Pharm. Sci., 2017, 96, 515-529.
[http://dx.doi.org/10.1016/j.ejps.2016.10.025] [PMID: 27777066]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy