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.