Silicone elastomer films loaded with 5-fluorouracil for time-dependent drug release

Silicone elastomer composite films loaded with the antitumor drug 5-fluorouracil (5-FU) were developed for controlled release applications. Polydimethylsiloxane (PDMSOH) films were crosslinked using tetraethoxysilane and room-temperature vulcanization catalysts, with glycerol incorporated as a hydrophilic modifier to regulate permeability of the hydrophobic silicone matrix. Dimethyl sulfoxide was used to solubilize 5-FU during film preparation. Film microstructure and drug distribution were analyzed by scanning electron microscopy and Raman spectroscopic imaging. Among the tested formulations, the film containing 30 wt.% glycerol (F-4) exhibited uniform drug distribution and the most favorable 5-FU release profile in 0.9% NaCl solution, consistent with its morphological characteristics. Cytotoxicity and cytocompatibility were assessed in A549 and HepG2 cells using an ISO 10993-5 extract test. Extracts from the blank F-4 film were minimal cytotoxic across all extraction times, whereas extracts from the 5-FU-loaded F-4 film produced a time-dependent reduction in cell viability in both cell lines. The extract-mediated cytotoxicity closely followed the UV-Vis release profile, indicating that the biological response was predominantly driven by time-dependent 5-FU release rather than film-derived leachables. Overall, glycerol-modified PDMSOH films provide a tunable platform for sustained 5-FU delivery.