Film-forming system of optimized tacrolimus-loaded nanostructured lipid carriers for effective topical treatment of atopic dermatitis

Abstract

Tacrolimus (TAC), a calcineurin inhibitor used topically for T-cell-mediated skin diseases, faces challenges due to poor solubility and limited skin penetration. To address these limitations, a film-forming system (FFS) incorporating nanostructured lipid carriers (NLCs) was developed for enhanced topical delivery. TAC-loaded NLCs (TAC-NLC) were prepared via high-temperature and high-pressure homogenization and optimized using Box-Behnken design. The optimized TAC-NLC showed 102.7 nm particle size, 0.126 PDI, 80.5 % encapsulation efficiency, and 2.5 % drug loading. TAC-NLC@FFS demonstrated spherical morphology and improved skin adhesion. In vitro studies showed sustained drug release and reduced cytotoxicity. In a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis model, TAC-NLC@FFS significantly reduced dermatitis scores compared to the negative control group (score at week 7: 3.5 ± 0.6 vs. 8.00 ± 1.2), with efficacy comparable to commercial ointments. Spleen weight, an indicator of systemic inflammation, was significantly reduced in all treatment groups, supporting anti-inflammatory activity. Additionally, serum IgE and IL-4 levels, key markers of allergic inflammation, were decreased in TAC-treated groups, with IL-4 reduction showing statistical significance. These findings suggest that TAC-NLC@FFS combines improved skin delivery and formulation stability with therapeutic efficacy, offering a promising strategy for the topical treatment of atopic dermatitis.