Design and characterization of κ-Carrageenan:PVA hydrogels to repurpose the topical delivery of betamethasone

Atopic dermatitis (AD) is a severe inflammatory skin disorder, affecting children and adults worldwide, and despite the several existing treatments, it is necessary to find new alternative topical therapies. Hydrogels may represent a good tool to treat AD due to their high water content, making them excellent candidates for drug delivery vehicles in skin research. This work aimed to develop and characterize hybrid hydrogels composed of gel-forming polymers (k-carrageenan and polyvinyl alcohol) for cutaneous delivery of betamethasone (up to 0.2 mg mL^-1) widely used to manage AD, with high skin retention. Bergamot oil and menthol essential oils were also incorporated into the hydrogels to study their effects on penetration and retention of the corticosteroid. Rheological properties revealed the pseudoplastic behavior of the hydrogels, a favorable characteristic for skin application. Cytocompatibility towards fibroblasts and keratinocytes was determined, revealing safe usage of the hydrogel blends up to 100 mg mL^-1, corresponding to 20 µg mL^-1 in betamethasone, but was compromised by the presence of the essential oils in the higher hydrogel tested concentrations (50 and 100 mg mL^-1). The ex vivo pig ear skin permeation assay showed that hydrogels promote betamethasone retention up to 20 % of the added dose (c.a. 10 µg) even after 24 h of permeation, independently of the use of essential oils' use in the composition, showing that they might be a good strategy to treat AD skin.