Brazilian Red Propolis Nanoparticles: In Vitro Anticancer Effects in Female-Associated Malignancies and In Vivo Toxicity in an Alternative Model.

This study explores the development and characterization of polymeric nanoparticles encapsulating Brazilian red propolis extract (BRPE) for application in ovarian (OVCAR-3) and breast (MDA-MB-231) cancers. The nanoparticles (NCBRPE), produced by nanoprecipitation, were evaluated for size, polydispersity index (PdI), zeta potential, and encapsulation efficiency (EE). Stability assessments over 365 days confirmed preserved physicochemical properties. Release kinetics, evaluated using a dialysis membrane assay and UPLC-MS, revealed that vestitol and formononetin followed the Peppas-Korsmeyer model, while biochanin A followed Higuchi kinetics, indicating diffusion-controlled mechanisms. Flow cytometry and confocal microscopy showed lower uptake of NCBRPE compared to free BRPE, though uptake was significantly higher in OVCAR-3 cells, suggesting receptor-mediated internalization. Cell cycle analysis revealed that NCBRPE, but not BRPE, induced a shift from G1 to S phase, potentially impairing cell proliferation. Migration assays demonstrated significant inhibition of OVCAR-3 cell migration by both BRPE and NCBRPE. Acute toxicity evaluation in Galleria mellonella confirmed the safety of NCBRPE, with over 80% survival at doses up to 50 mg/kg. These results demonstrate that nanoencapsulation enhances the stability, release control, and therapeutic activity of BRPE, supporting its potential as a multifunctional nanoplatform for treating female cancers, particularly ovarian carcinoma.