Topical delivery of fluocinolone acetonide integrated NLCs and salicylic acid enriched gel: A potential and synergistic approach in the management of psoriasis

Abstract

Psoriasis is a chronic autoimmune inflammatory disease of the skin that tends to affect around 2–3% of the global population. As a cascade of events occurs concurrently during psoriasis pathogenesis, treatment with a therapeutic combination is primarily concerned. The conventional formulation containing a combination of anti-inflammatory corticosteroid and the keratolytic agent is frequently employed for topical therapy of psoriasis, but their efficacy remains low. Therefore, the present work aimed to explore the efficacy of Fluocinolone Acetonide (FA) loaded NLCs and plain Salicylic Acid (SA) containing novel gel (FSG) for effective management of psoriasis. For comparative study plain FA, and SA containing conventional gel (PFSG) formulation was also prepared. The FSG formulation exhibited prolonged release of FA for more than 24 h, whereas the PFSG formulation released more than 90% of FA within 7 h. Ex-vivo permeation study revealed negligible absorption of drugs into the systemic circulation from both the FSG and PFSG formulations; nevertheless, the dermal pharmacokinetic investigation revealed significantly higher (P < 0.05) retention of FA from FSG formulation as compared to PFSG formulation. Confocal laser scanning microscopic study confirmed strict confinement of FA loaded NLCs to the epidermal and deep dermal layer of the skin whereas PFSG was largely restricted to the outer layer of skin. No skin irritation was reported in vivo, upon topical application of FSG formulation, whereas slight irritation was reported for PFSG formulation. Results of histopathological studies proposed that FSG could effectively alleviate the psoriatic manifestations in the IMQ prompted model. This examination was additionally aligned with PASI scoring. Further, the findings of the ELISA study revealed that the FSG significantly reduced the concentration of prime pathogenic cytokines (TNF-α, IL-17, and IL-22) as compared to PFSG and IMQ groups. Thus, the overall findings suggest greater efficacy of nanocarrier enriched gel formulation than plain gel formulation.