Development and Characterization of Polylactic Acid-Resveratrol-Based Polymeric Nanoparticles and Their Cytotoxic Effect on Two Breast Cancer Cell Lines in Combination with Doxorubicin

Background/Objectives: Resveratrol (RSV) is a phenolic compound that possesses antioxidant properties and whose biological application has been limited by its physicochemical properties, including its low solubility and stability. Methods: In this study, polymeric nanoparticles (NPs) were developed using polylactic acid (PLA) to encapsulate resveratrol and improve its bioavailability, using a factorial design to optimize the formulation and evaluate its cytotoxicity against breast cancer cells. Results: The optimized system presented an average size of 389.2 nm, a PDI of 0.127, a negative z-potential, and an encapsulation efficiency of 76.02%. The statistical analysis indicated that the PLA: RSV ratio was the main determinant of encapsulation percentage and particle size (p < 0.05). On the other hand, with the hemolysis test, blood compatibility was evidenced at all concentrations evaluated, while in the cell assays, the PLA-RSV nanoparticles significantly decreased the cellular viability of MCF-7 and MDA-MB 231 cells compared to untreated cells, and in combination with NP PLA-RSV and doxorubicin, greater cytotoxicity was produced in MCF-7 cells compared to nanoparticle-only treatments (p < 0.05, ANOVA, via followed by a Fisher test). Conclusions: In addition, distinct cytotoxic effects are observed, associated with their tumor phenotype. Taken together, these results suggest that PLA-RSV NPs are a useful system for future studies on redox status and other biological processes important in cancer.