Nano-Based Hydrogel for Cutaneous Sesamol Delivery in UVB-Induced Skin Injury

Dexamethasone, a glucocorticoid, is used to mitigate UVB radiation-induced skin inflammation. Nevertheless, its continuous use has been linked to adverse effects. Sesamol, a compound with promising pharmacological properties, faces a challenge due to its rapid skin permeation, which limits its effectiveness when administered cutaneously. Consequently, polymeric nanocapsules have emerged as a technological solution to enhance the skin residence time and efficacy of sesamol in topical applications. This study details the preparation of sesamol-loaded ethylcellulose nanocapsule suspensions and evaluates their in vitro cytotoxicity against keratinocyte and fibroblast cell lines using the MTT assay. The results show that while free sesamol reduced the viability of 3T3 fibroblast cells, this cytotoxic effect was mitigated upon nanoencapsulation. In HaCaT cells, only the highest concentration of nanoencapsulated sesamol exhibited a moderate cytotoxic effect. A nano-based hydrogel containing 1 mg/g of sesamol and 2.5% guar gum was formulated for cutaneous application. The hydrogel's pharmacological efficacy was assessed in an in vivo sunburn model induced by UVB light in Swiss mice, demonstrating that the sesamol-loaded nanocapsules significantly attenuated inflammatory responses, as evidenced by a reduction in ear thickness and polymorphonuclear cell infiltration. Furthermore, ex vivo permeation studies on UVB radiation-injured human skin confirmed that nanoencapsulation markedly reduced the permeation rate of sesamol through the skin's layers. The hydrogels were also found to be bioadhesive to human skin. In conclusion, the hydrogel containing sesamol-loaded nanocapsules presents a promising therapeutic approach for treating inflammatory skin conditions, including sunburn.