Development of Topical Nanoformulations for the Treatment of Atopic Dermatitis

Abstract

newlineThe skin disease like Atopic dermatitis (AD) is a repetitive inflammatory skin disease. Major symptoms of AD includes xerosis, eczematous lesions, pruritus, and high serum immunoglobulin (IgE) levels. This results in itching and scratching which causes mechanical skin injury. Acute AD skin lesions exhibit helper T cell (Th2) dominant inflammation indicated by dermal infiltration of CD4+ T cells and eosinophils. This results in increased mast cells, deposition of collagen and dermal thickening. newlineTopical corticosteroids and calcinurin inhibitors (CIs) like sirolimus and tacrolimus in formulations like ointment, cream, lotion, oral formulations, IM/IV are currently used. Amongst all these drugs, steroids are preferred drugs but potent steroids causes hypertrophy of the skin. Hence, tacrolimus or sirolimus are preferred over the steroids for the treatment of acute or chronic dermatitis. Tacrolimus (TLS) is approved by USFDA to be used in the treatment of atopic dermatitis. Therapeutic use of TLS is complicated due to its narrow therapeutic index and poor solubility in water. This strongly indicates need to develop suitable formulation, which could cure the same. newlineTo overcome the problem of solubility and skin targeting, materials can be transferred into the nano-dimension which will change their physical properties. Previously solid lipid nanoparticles, nano lipid carriers, nanosuspension, etc are formulated but no product is available in market due to some incompatibility issues. Nanocrystal (NC) is one of the approach to improve solubility and thereby bioavailability of the poorly soluble drug. NC possess advantages like minimal risk of incompatibility with excipients, 100% drug loading and ease of scalability. As another approach, mesoporous silica nanoparticles (MSNs) were selected which has attracted a lot of attention as multifunctional nanocarrier for many BCS class II and IV drugs. This is due to their unique properties such as ordered porous structure, tunable size, high surface area, biocompatibili