Blended polymeric films containing the drugs simvastatin and resveratrol: The supersaturation approach for melanoma treatment

In this study, blended films of simvastatin (SIM) and resveratrol (RESV) were developed to improve the release of both poorly soluble drugs, aiming for the topical treatment of melanoma. RESV films containing different plasticizer content (polysorbate 80) exhibited residual crystals in the polymeric matrix of Eudragit®RL. The addition of the second drug (SIM) to blended films improved miscibility/solubility of RESV in the polymeric matrix, avoiding recrystallization of both drugs, as well as affecting intermolecular interactions of film components. Release investigations showed that RESVSIM-blended films provide higher drug release than RESV films and crystalline drugs in acidic buffer, but similar release to crystalline drugs in the same buffer at physiological pH. Cell culture studies revealed a cytotoxic synergistic effect of RESV and SIM in melanoma cell lines. The blended film RESVSIM3 and a blank film showed greater viability reduction in melanoma cell lines compared to a non-tumoral melanocyte cell line.