Multifaceted targeting of cationic liposomes via co-delivery of anti-IL-17 siRNA and corticosteroid for topical treatment of psoriasis

Abstract

Psoriasis is a chronic autoimmune disorder that affects the skin to alter its structure and physiology and express the phenotypic function of abnormal epidermal cell growth through a cascade of molecular, and cellular intervention. The histological changes in skin include inflammation, scaling, hyperproliferation of epidermis resulting in thickening of the skin, under the influence of altered immunopathogenesis. The zone of activity for the therapeutic targeting of psoriasis is viable epidermis involving various cellular events regulating the whole progression of the disease manifestation. Therefore, therapeutic targeting of psoriasis through the systemic route would be imprecise and associated with numerous side effects. Small interfering RNA (siRNA) molecules have emerged as a powerful class of therapeutics for treating psoriasis. However, successful targeted delivery of necked siRNA into the skin is hampered due to physicochemical features, proneness to enzymatic degradation, and unavailability of effective delivery carriers. The steroidal medications are the most preferred choice among existing conventional topical formulations; however, they also have their drawbacks like poor aqueous solubility, deprived drug penetration across the skin, reduced half-life, dose-dependent side effects, and reduced patient compliance. In the present study, we hypothesize the development of a liposomal gel formulation for co-delivery of siRNA (siRNA against IL-17A) and a steroidal drug (Clobetasol propionate) to target different pathogenic events of psoriasis leading to the accomplishment of synergistic therapeutic effect. Since a sequence of events simultaneously occurs during the pathogenesis of psoriasis, synergistic blends of siRNA and corticosteroid would ensure a multi-targeted treatment that would act through a diverse range of mechanisms, ultimately leading to the enhancement of therapeutic effect. Therefore, exploiting the full therapeutic potential of these therapeutics. Thus, the present work suggests a novel, innovative, and promising idea for accomplishing effective treatment of psoriasis.