A study design and development of roflumilast topical nano carrier using silver nanoparticles for the treatment of psoriasis in animal model

Abstract

xv newlineABSTRACT newlinePsoriasis is a chronic, immune-mediated inflammatory skin disorder characterized by hyperproliferation of keratinocytes, erythema, and scaling. Conventional therapies often provide limited relief and may be associated with adverse effects or poor patient compliance. To overcome these limitations, the present research focuses on the development of a novel topical nanocarrier system incorporating roflumilast-loaded silver nanoparticles (RAgNPs) for enhanced and targeted psoriasis therapy. newlineThe study was initiated with the synthesis of silver nanoparticles using a Box- Behnken design to optimize formulation parameters. The physicochemical characterization of the developed nanoparticles was performed using techniques such as particle size analysis, zeta potential, transmission electron microscopy, and drug entrapment efficiency. Additionally, molecular docking studies were conducted to understand the binding affinity of roflumilast with relevant inflammatory targets. newlineThe optimized nanoparticles were incorporated into a cream base to develop a topical formulation. This formulation was evaluated for its antimicrobial, anti- inflammatory, and cytotoxic effects on L929 fibroblast cell lines using Trypan Blue and MTT assays. Further, in vivo studies were carried out on BALB/c mice, including acute dermal toxicity studies following OECD guidelines and anti-psoriatic activity assessment using imiquimod-induced psoriasis-like dermatitis. newlineThe efficacy of the formulation was evaluated using PASI scoring and histopathological analysis. The developed RAgNP cream exhibited significant anti- psoriatic activity with minimal toxicity and high skin compatibility, suggesting its potential as a promising candidate for safe, effective, and sustained topical treatment of psoriasis newlineKEYWORDS: Box-Behnken design, Conventional therapies, Psoriasis, Roflumilast and Sustained topical treatment. newline