Atopic dermatitis (AD) is a persistent inflammatory condition that has a strong correlation with oxidative stress. Histopathological hallmarks include spongiosis, epidermal hyperplasia and prominent inflammatory infiltrate. Itching, impaired skin barriers, and immunological deviations are typical symptoms of AD and are reported to be by astaxanthin (AST) a tetraterpenoid extracted from microorganisms, sea life including salmon, shrimp, krill, lobster, and bacteria and a few plants [1,2]. Research has shown that AST holds promise as a supportive skin care treatment in AD. It can inhibit lipid peroxidation, increase cAMP levels, inhibit inflammation, inhibit proinflammatory biomarkers such as IL-1β, IL-4, IL-5, and TNF-α, block NF-κB, inhibit cyclooxygenase, iNOS, prostaglandin E2, reduce serum IgE level, reduce eosinophils numbers, attenuate mast cells degranulation and activate the Nrf2/HO-1 antioxidant pathway [2]. In addition, AST has various cosmetic benefits such as improvement of skin elasticity, skin texture, and moisture content of the corneocyte layer (terminally differentiated keratinocytes). Thus, topical application of AST on AD lesions is beneficial as it might lead to improved contact time and prolong symptom-free periods in AD therapy [3].

AST molecule has poor aqueous solubility (83 μg/mL), and high lipophilicity (log p > 10.3) which not only makes its absorption across the epidermis difficult but also presents formulation challenge. Besides, it is also prone to photodegradation and aggregate formation. To address these issues, an effective delivery system is desired. AST has previously encapsulated for topical applications using various nanocarriers viz. liposome [4], nanoemulsion [5], nanoparticle [6], NLC [7], SNEDDS [8], and nanocapsules [3]. Nano-flexible membrane vesicles (FMVs) dispersed in the hydrophilic polymeric matrix may be used to administer AST to deeper layers of the skin, wherein, several types of innate immune cells reside. The FMVs are soft malleable vesicles, having the ability to squeeze themselves across the tissue, and achieve desirable dermal permeation due to the presence of an edge activator in its formula. Such formulations are widely approved by US FDA, owing to the biocompatible components like phospholipid in their composition. These protect unstable compounds against degradation. Further Carbopol gel, promises good moisturizing ability, viscosity, skin adherence, occlusive effect, and increased therapeutic effect. It is popular as a polymeric base in cosmetics, pharmaceutical products and is compatible with wide variety of agents. Thus the aim of the present research work was to develop and optimize AST loaded FMVs (AST-FMVs) hydrogel using response surface methodology (RSM) to enhance effectiveness against AD, by increasing permeability and solubility across the skin-barrier. The best optimized FMV formula after loading into Carbopol hydrogel (1 %) was evaluated for its therapeutic efficacy in the hapten-induced AD model.