Methotrexate-Loaded Nanostructured Lipid Carrier Gel Alleviates Imiquimod-Induced Psoriasis by Moderating Inflammation: Formulation, Optimization, Characterization, In-Vitro and In-Vivo Studies
Yogeeta O Agrawal,1 Umesh B Mahajan,2 Hitendra S Mahajan,1 Shreesh Ojha3 1Department of Pharmaceutics and Quality Assurance, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra 425405, India; 2Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Educat...
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2020
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| Acceso en línea: | https://doaj.org/article/9f05d042637a4ed1b87661a8b06420fd |
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| Sumario: | Yogeeta O Agrawal,1 Umesh B Mahajan,2 Hitendra S Mahajan,1 Shreesh Ojha3 1Department of Pharmaceutics and Quality Assurance, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra 425405, India; 2Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra 425405, India; 3Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab EmiratesCorrespondence: Yogeeta O AgrawalR. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, District-Dhule, Maharashtra 425405 Tel +02563 255189 (Office)Email goyalyogita@rediffmail.comIntroduction: Methotrexate exhibits poor cutaneous bioavailability and systemic side effects on topical administration, so there is an unmet need for a novel carrier and its optimized therapy. Methotrexate-loaded nanostructured lipid carriers (MTXNLCs) were formulated and characterized to determine in vitro drug release and evaluate the role of MTXNLC gel in the topical treatment of psoriasis.Methods: A solvent diffusion technique was employed to prepare MTXNLCs, which was optimized using 32 full factorial designs. The mean diameter and surface morphology of MTXNLCs was evaluated. The crystallinity of lyophilized MTXNLCs was characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). MTXNLCs were integrated in 1% w/w Carbopol 934 P gel base, and in vitro skin deposition studies in human cadaver skin (HCS) were carried out.Results: The optimized MTXNLCs were rod-shaped, with an average particle size of 253 ± 8.65 nm, a zeta potential of − 26.4± 0.86 mV, and EE of 54.00± 1.49%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of MTX was found in HCS from MTXNLC gel (71.52 ± 1.13%) as compared to MTX plain gel (38.48± 0.96%). In vivo studies demonstrated significant improvement in therapeutic response and reduction in local side effects with MTXNLCs-loaded gel in the topical treatment of psoriasis. Anti-psoriatic efficacy of MTXNLCs 100 ug/cm2 compared with plain MTX gel was evaluated using imiquimod (IMQ)-induced psoriasis in BALB/c mice. The topical application of MTXNLCs to the mouse ear resulted in a significant reduction of psoriatic area and severity index, oxidative stress, inflammatory cytokines like TNF-α, IL-1β, and IL-6 and IMQ-induced histopathological alterations in mouse ear samples.Conclusion: Developed formulation of MTXNLC gel demonstrated better anti-psoriatic activity and also displayed prolonged and sustained release effect, which shows that it can be a promising alternative to existing MTX formulation for the treatment of psoriasis.Keywords: methotrexate, nanostructured lipid carriers, Capmul MCM, Compritol 888, psoriasis, IMQ |
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