Delivery of 3-O-Ethyl-L-Ascorbic Acid from Radiation-Crosslinked Hydrogels to Promote Extracellular Matrix Production in Fibroblasts

L-ascorbic acid is a bioactive compound widely used in dermatology and cosmetology, owing to its antioxidant properties and essential role in collagen biosynthesis. However, its poor chemical stability in aqueous formulations considerably limits its incorporation into hydrogel-based delivery systems. In the present study, a radiation-crosslinked hydrogel based on poly(N-vinylpyrrolidone), poly(ethylene glycol) and agar was developed as a carrier for 3-O-ethyl-L-ascorbic acid (EvitC), a stabilized vitamin C derivative, for topical application. The influence of EvitC on hydrogel formation, physicochemical properties, release characteristics and long-term stability was investigated. In parallel, the biological safety and activity of EvitC and EvitC-containing hydrogel were evaluated using human dermal fibroblasts. Cell metabolic activity was assessed using the XTT assay and further supported by the qualitative evaluation of cell viability using Live/Dead staining, while extracellular matrix production was assessed using the Col-F assay. Hydrogels containing 0.1% EvitC exhibited advantageous essential properties, such as gel fraction, swelling capacity and mechanical properties while maintaining the sustained release of the biologically active compound. The components of the hydrogel matrix effectively protected EvitC during radiation processing and storage, thereby confirming the overall stability of the formulation. Neither EvitC nor hydrogel extracts induced cytotoxic effects under all tested conditions. Furthermore, the prolonged exposure of fibroblasts to hydrogel extracts resulted in a moderate but statistically significant increase in ECM-associated Col-F, i.e., collagen- and elastin-associated fluorescence. These findings support the potential of the developed radiation-crosslinked hydrogel as a stable and cytocompatible platform for the topical delivery of EvitC. The combination of favorable physicochemical properties, formulation stability and excellent biological performance highlights its potential for the development of advanced hydrogel-based skin care formulations.