A dual-strategy nanocomposite hydrogel platform of nanosuspensions and deformable liposomes for enhanced curcumin delivery against skin cancer cells

Patient outcomes in skin cancer are compromised by invasive treatments, demanding a paradigm shift toward effective, non-invasive strategies. This study aimed to develop dual-strategy nanocomposite hydrogel platforms for enhanced, localized delivery of curcumin against skin cancer cells. Two distinct nanocarriers, curcumin nanosuspensions (CUR-Ns) and curcumin liposomes (CUR-Lip), were engineered and embedded within a bioadhesive Gantrez™/gelatin hydrogel. Anticancer activity, cellular uptake, and apoptosis induction were assessed in A431 skin cancer cell line. Nanocomposite hydrogels were fabricated by EDC/NHS crosslinking, with nanocurcumin pre-mixed in gelatin to ensure uniform dispersion. Ex vivo skin permeation was evaluated using Franz diffusion cells with neonatal porcine skin. Both formulations demonstrated potent anticancer activity against A431 cells, with CUR-Lip (IC₅₀ = 9.32 µg/mL) and CUR-Ns (IC₅₀ = 13.43 µg/mL) dramatically outperforming free CUR (IC₅₀ = 44.73 µg/mL) while maintaining excellent biocompatibility. Physicochemical characterizations of the hydrogel demonstrated high moisture content, fluid absorbency, and adequate mechanical strength. These favorable properties facilitated effective delivery. Crucially, the nanocarriers displayed unique therapeutic kinetics. CUR-Ns provided a rapid onset of action, characterized by faster initial skin permeation. In contrast, CUR-Lip offered superior sustained efficacy, showing greater cytotoxicity, and achieving significantly higher cumulative skin deposition, with a transdermal flux of 105.52 ng/cm²/h. The hydrogel platform successfully preserved these distinct permeation profiles, confirming its utility as a versatile delivery vehicle. This dual-strategy approach enables tailored curcumin delivery offering either rapid or sustained release and represented a significant advancement in developing non-invasive therapies for skin cancer.