Biopolymeric Films from the White Rind of Watermelon (Citrullus lanatus) for Localized 5‑Fluorouracil Application

In this study, we developed biopolymeric films derived from watermelon white rind (WF) as a platform for the localized delivery of 5-fluorouracil (5-FU). The films were obtained by solvent casting and subjected to comprehensive physicochemical characterization, confirming the successful incorporation of 5-FU and the biocompatibility of the control WF films. Biological assays were performed using murine melanoma (B16-F10) and human keratinocyte (HaCaT) cell lines. WF-5FU films significantly reduced the cell viability, clonogenic survival, and migration in both models. The cytotoxic effects were more pronounced in B16-F10 cells, confirming their higher sensitivity to the treatment. The micronucleus (MN) assay revealed a concentration-dependent increase in mutagenicity, consistent with the known genotoxic profile of 5-FU. Control films did not induce cytotoxic or genotoxic effects. Overall, WF-based biopolymeric films demonstrated favorable safety in the absence of drug loading and exhibited antitumor activity when loaded with 5-FU. These findings support their potential as a sustainable and effective topical delivery system for localized skin cancer therapy. Further in vivo and clinical investigations are needed.