Abstract
Methotrexate (MTX), the gold standard against psoriasis, poses severe problems when administered systemically viz increased toxicity, poor solubility and adverse reactions. Hence, a topical formulation of MTX for the management of psoriasis can be an effective approach. The present study aimed to develop an MTX based nanoparticle-loaded chitosan hydrogel for evaluating its potential efficacy in an imiquimod-induced psoriatic mice model. MTX-NPs loaded hydrogel was prepared and optimized using the o/w emulsion solvent evaporation method. Particle size, zeta potential, entrapment efficiency, in vitro drug release, ex vivo permeation, skin irritation and deposition studies were performed. Psoriatic Area and Severity Index (PASI) score/histopathological examinations were conducted to check the antipsoriatic potential of MTX-NPs loaded hydrogel using an imiquimod (IMQ)-induced psoriatic model. Optimized MTX-NPs showed a particle size of 256.4 ± 2.17 nm and encapsulation efficiency of 86 ± 0.03%. MTX-NPs loaded hydrogel displayed a 73 ± 1.21% sustained drug release in 48 h. Ex vivo permeation study showed only 19.95 ± 1.04 µg/cm2 of drug permeated though skin in 24 h, while epidermis retained 81.33% of the drug. A significant decrease in PASI score with improvement to normalcy of mice skin was observed. The developed MTX-NPs hydrogel displayed negligible signs of mild hyperkeratosis and parakeratosis, while histopathological studies showed healing signs of mice skin. So, the MTX-NPs loaded hydrogel can be a promising delivery system against psoriasis.
Highlights
Psoriasis, an inflammatory disease of the skin with completely unknown cause, is aT-cell mediated autoimmune chronic disorder of hyper-activated keratinocytes [1]
Methotrexate was encapsulated into pH sensitive polymeric NPs of E100, and the prepared NPs were loaded into the hydrogel
Methotrexate nanoparticles (MTX-NPs) were optimized for the enhancement of solubility and better skin deposition to gain the better therapeutic benefits of MTX to manage psoriasis
Summary
An inflammatory disease of the skin with completely unknown cause, is aT-cell mediated autoimmune chronic disorder of hyper-activated keratinocytes [1]. An inflammatory disease of the skin with completely unknown cause, is a. The overexpressed proinflammatory cytokines and chemokines produced by Th1 cells make this disease a multifactorial disorder. These Th1 cells are primarily responsible for the production of tumor necrotic factor alpha (TNF-α) and cytokines, i.e., interleukins (IL)–6, IL- 17, IL–22 and IL–23 [2]. These cytokines and chemokines together result in autoamplification and hyper-proliferation of the epidermis, along with cutaneous inflammation and dermal neovascularization, leading to the formation of plaque psoriasis [3]. Genetic factors are mainly responsible for the emergence of this disease as it is noncontagious
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