Topical astaxanthin via nano flexible membrane vesicles: A new paradigm in atopic dermatitis treatment with immunomodulatory and anti-inflammatory benefits

Atopic dermatitis (AD) is a frequently encountered chronic inflammatory disease that primarily afflicts children and involves activation of the Th2 immune response. For topical management of AD, poorly soluble molecule astaxanthin (AST) was efficiently encapsulated in flexible membrane vesicles (FMVs) and subsequently dispersed in a Carbopol® based hydrogel to achieve comparable efficacy to crude drug and Talimus® 0.1 % (that is used as a benchmark for AD treatment). Vesicles prepared using rotary film evaporation and optimized through face central composite design had a mean particle size of 194.9 nm, PDI value of 0.239 entrapment efficiency of 74.49 ± 9.95 %, skin retention of 25.84 ± 6.44 %, and% skin permeation of 1.63 ± 0.56 %. AST-loaded optimized FMVs, gelled for topical application exhibited good consistency and adhesion to the skin. DSC and FTIR studies confirmed a positive interaction of the components in FMVs and AST-FMV loaded Carbopol gel. The rheological study of the hydrogel demonstrated its thixotropic behavior and good spreadibilty. The effect of the optimized formulation was evaluated on 2,4-dinitrochlorobenzene-induced AD-like lesions in Balb/C mice by analyzing morphological and histopathological changes which showed improvement. Also, the levels of AD-related cytokines in the skin tissue were measured and found to decline after treatment with hydrogel. Immunoglobulin E concentration and leukocyte count in the serum also diminished subsequent to use of hydrogel. In-vivo evaluation showed AST-FMV hydrogels lessened inflammatory cells in the blood, enhanced macroscopic alterations, and diminished IL-4, IL-5, and IFN-γ levels in comparison to the diseased group. These results corroborated the premise that formulating AST-FMV hydrogel improves the anti-AD efficacy of AST.