Sodium Alginate Nanogels Encapsulating Cholecalciferol (Vitamin D3): A Topical Therapeutic Approach Targeting LOX IMVI and A431 Skin Cancer Cells.

The study explores sodium alginate nanogels encapsulating cholecalciferol (vitamin D3) as a novel topical therapeutic for skin cancer, targeting LOX IMVI (melanoma) and A431 (epidermoid carcinoma) cell lines. Nanogels were prepared using magnetic stirring and sonication, resulting in a uniform dispersion and enhanced stability. Physicochemical characterization revealed a particle size of 67.6 ± 13.43 nm, a polydispersity index (PDI) of 0.30 ± 0.02, and a ζ-potential of -25.00 ± 2.00 mV, confirming good colloidal stability and suitability for topical application. In vitro drug release studies demonstrated a sustained-release profile, with 89.73 ± 2.1% cholecalciferol released over 34 h, as predicted by a first-order kinetic model (R 2 = 0.9871). Cytotoxicity assays showed significant anticancer activity, with IC50 values of 29.51 ± 1.56 and 24.95 ± 1.32 μM for LOX IMVI and A431 cell lines, respectively, while exhibiting reduced cytotoxicity against normal HSF cells (IC50 = 83.88 ± 4.43 μM). Cell-cycle analysis indicated G1/S phase arrest, and Annexin V-FITC/PI staining confirmed apoptosis induction with minimal necrosis. Molecular docking studies validated the mechanism of action, revealing strong binding of cholecalciferol to the vitamin D receptor (VDR) through hydrogen bonding with SER278 and SER275, π-cation interaction with TRP286, and hydrophobic interactions, with a docking score of -11.7 kcal/mol. These findings suggest sodium alginate nanogels encapsulating cholecalciferol as a promising, biocompatible therapeutic for the topical treatment of skin cancer, paving the way for future clinical investigations.