Tofacitinib laden MCM-48 mesoporous silica nanogel for topical psoriasis: ex vivo and in vivo therapeutic validation.

Abstract

Psoriasis is a chronic immune-mediated inflammatory skin disorder wherein conventional therapies are frequently constrained by poor percutaneous absorption, high recurrence rates, and systemic or steroid-induced adverse effects. This study developed Tofacitinib-loaded MCM-48 mesoporous silica nanoparticles (TFC-MCM-48) incorporated into a Carbopol hydrogel as a topical nanocarrier system for controlled TFC delivery. Blank MCM-48 MSNs were optimized using a Box-Behnken design, followed by TFC loading through modified solvent evaporation and hydrogel formulation. A validated RP-HPLC method was used for TFC quantification. The optimized blank MCM-48 exhibited particle size of 251.8 ± 12.3 nm (PDI 0.172 ± 0.02), shifting to 311.6 ± 17.2 nm (PDI 0.326 ± 0.03) upon drug loading. Nitrogen adsorption porosimetry and low-angle XRD supported TFC incorporation with retention of the ordered mesoporous architecture and reduced drug crystallinity. The formulated TFC-MCM-48 gel was homogeneous, with a viscosity of 27,800 ± 225 cP and spreadability of 16.91 ± 0.24 g·cm/s, providing sustained in vitro release of ∼54% and greater ex vivo permeation across excised skin of ∼50% over 12 h, which maintained the physicochemical and release performance across three months of storage. In a cyclophosphamide-imiquimod-induced psoriasiform BALB/c mouse model, TFC-MCM-48 gel significantly outperformed pure drug gel, achieving a ∼92% reduction in PASI score than disease control, reducing epidermal thickness and Baker's histopathological score. This recovery was accompanied by marked attenuation of serum C-reactive protein, splenomegaly, and liver weight indices, with improved skin and spleen histology. These findings highlight TFC-MCM-48 hydrogel as a promising topical nanoplatform for Psoriasis management.

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