Elaboration of novel gel-core oleosomes encapsulating phytoconstituent for targeted topical delivery in a vitiligo-induced mouse model: Focus on antioxidant and anti-inflammatory pathways

Berberine (BER) is a natural isoquinoline with promising antioxidant and anti-inflammatory effects. However, BER's low permeability hampers its topical utilization. This study aimed to elaborate and assess a novel hyaluronate integrated gel-core oleosomes nanovesicular system to ameliorate BER's dermal availability for targeted topical vitiligo treatment. Sodium hyaluronate and sodium oleate were selected as natural biological key components for their excellent skin-penetrating characteristics. Berberine-oleosomes (BER-OS) were prepared using a modified ethanol injection technique. Ex-vivo studies were performed using full-thickness human skin for simulating the real topical application. Also, in-vivo pharmacodynamic studies were conducted using a vitiligoinduced mice model. The antioxidant and anti-inflammatory effects were evaluated using depigmentation area scoring, biochemical, and gene-expression studies. BER-oleosomes attained a small particle size (186 +/- 4) nm, high zeta potential (-36.0 +/- 1.13) mV, excellent entrapment efficiency % (92.3 +/- 0.67), outstanding sustained release of 45% after 24 h, and high physical stability. Ex-vivo study emphasized the significant capability of hyaluronate-integrated gel-core oleosomes to enhance BER retention in the human skin, enabling the effective local targeted treatment of vitiligo with minimal systemic side effects. Moreover, results displayed significant augmented anti-inflammatory and antioxidant actions for BER-oleosomes compared to BER-conventional gel. Interestingly, placebo-oleosomes possessed a significant intrinsic effect against vitiligo. Histological, immunohistochemical, and toxicological investigations confirmed BER-oleosome's safety and efficacy. Conclusively, novel BER-loaded gel-core oleosomes were considered a promising nano-topical targeted approach that overcomes delivery obstacles for vitiligo treatment.