Development and In Vitro/In Vivo Evaluation of pH-Sensitive Polymeric Nanoparticles Loaded Hydrogel for the Management of Psoriasis

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.

pH-Responsive Polymer Nanomaterials for Tumor Therapy

“…Researchers have designed pH-responsive polymer nanomaterials (10–100 nm) ( 33 ) that can be engineered to suit the need of the therapy and target area. These materials are relatively stable in the blood and normal tissue but are unstable in the tumor area (acidic pH), leading to rapid changes in the degree of ionization in pH-responsive groups, causing material changes that release the anti-tumor drugs, achieving the goal of targeted tumor therapy ( 34 , 35 ). Researchers have performed sustainable research on these pH-responsive polymer nanomaterials ( 36 , 37 ).…”

The Anti-Psoriatic Efficacy and Safety Profile of Topical and Intralesional Methotrexate: A Literature Review

“…MTX in carbopol gel and carbopol gel treated groups exhibited features of psoriasis histology such as regular acanthosis, intraepidermal neutrophilic abscess. Cytokines : - - Local AE: No - Systemic AE: No Asad et al (2021) 32 25 a) MTX nanoparticles embedded into chitosan hydrogel b) Free MTX hydrogel c) Marketed cream d) Imiquimod cream e) Normal control 10 days Clinical : PASI score was decreased in group a-c, but a mark decreased was observed in group a Histology : Group a-c displayed the improvement in psoriatic lesion. Group b showed decrease in the thickness of both the dermis and epidermis but leukocytic infiltrations were present.…”

Latest on biomaterial-based therapies for topical treatment of psoriasis

“…The hybrid system possesses the advantages of various materials, exhibiting a promising prospect in the psoriasis management. 41,129,130 In one study, cellulose nanofiber (CNF) films were prepared using a vacuum filtration method for topically delivering curcumin-loaded nanostructured lipid carriers (NLCs) to a mouse model of psoriasis. 40 The CNF film in this system played an important role in not only delivering drugs, but also improving and maintaining skin hydration through occlusive effects when tightly adhered to the skin surface (Fig.…”