Niosomal gel improves dermal delivery of nimbolide: a promising approach for treatment of psoriasis

<b>Aim:</b> Psoriasis is a chronic inflammatory skin disorder characterized by the excessive proliferation of keratinocytes, forming thickened skin plaques due to immune-mediated cytokine responses. Delivering drugs through this barrier to target inflamed tissues remains challenging. Nimbolide (NIM), known for its anti-inflammatory and anticancer properties, shows promise in managing psoriasis. However, its efficacy is limited by its inability to penetrate the thickened horny layer of the skin. To overcome this obstacle, we have developed Nim-loaded niosomal (Nio) formulations (NIM Nio) aimed at improving dermal delivery and achieving localized sustained release at psoriasis-affected sites. <b>Methods:</b> The formulation characteristics were assessed using Zeta sizer, Transmission Electron Microscopy (TEM), and High-performance liquid chromatography (HPLC). The optimized formulation was evaluated for anti-psoriatic potential compared to Nim alone by using molecular techniques such as Confocal Microscopy, Flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Western blotting. <b>Results:</b> NIM Nio showed effective penetration into psoriatic skin, resulting in reductions in keratinocyte hyperproliferation, oxidative stress, splenomegaly, inflammatory cytokines, Psoriasis Area and Severity Index (PASI), and rete ridges compared to NIM alone. <b>Conclusion:</b> Our findings underscore the significant anti-proliferative, antioxidant, and anti-inflammatory properties of NIM Nio in psoriasis, demonstrating its potential as a promising therapeutic option for this challenging condition. Psoriasis is a chronic autoimmune disease characterized by abnormal inflammation and hyperplasia of epidermal keratinocytes, resulting in thickened skin with silvery scales. Nimbolide (NIM) has potent anti-inflammatory and anticancer properties, showing protective effects in psoriasis. NIM faces challenges in permeating thickened psoriatic skin, particularly the stratum corneum. Nimbolide loaded niosomal (NIM Nio) formulations aim to enhance delivery, promote dermal penetration and sustain drug release in psoriasis-affected sites. NIM Nio efficiently entraps NIM, reducing both cellular and mitochondrial reactive oxygen species (ROS) generation and hyperproliferation of keratinocytes by inducing apoptosis. Treatment with NIM Nio significantly reduces psoriatic severity, including skin redness, scaling and thickness and mitigates splenomegaly, along with inhibiting phosphorylation of inflammatory mediators such as NF-κB, MAPKs and STAT3, induced by EGF and IMQ.