Synergistic apoptotic effects of berberine and hesperidin co-encapsulated in PLGA nanoparticles on lymph node carcinoma of prostate cell line.

Natural origin therapeutic agents have recently gained attention as a promising cancer treatment approach. However, achieving effective therapeutic results depends on improving the pharmacokinetic properties of these compounds using new delivery systems. In this study, the simultaneous encapsulation of berberine and hesperidin in poly(lactic-co-glycolic acid)(PLGA) nanoparticles utilizing the double emulsion-solvent evaporation technique and the evaluation of their effects on the viability and induction of apoptosis in prostate cancer cells were investigated. The produced nanoparticles were characterized in terms of size, dispersion index, morphology, FT-IR analysis, encapsulation efficiency, and drug release profile. Prostate cancer cells (LNCaP) were cultured and treated with various concentrations of hesperidin and berberine in nanoencapsulation and free forms. The results showed that all produced nanoparticles had an average diameter below 200 nm, a uniform size distribution below 0.1, and a favorable encapsulation efficiency. According to the MTT test results, the application of nanoparticles resulted in a significant reduction in cell viability compared to the free form, which occurred in a dose-dependent manner. Flow cytometry and qRT-PCR analysis showed that hesperidin and berberine in nano form and combination had the greatest anti-cancer effects. In the comparison between hesperidin and berberine, too, berberine showed stronger anti-proliferative and apoptotic effects than hesperidin. The findings from the LDH and clonogenic assays also confirmed the apoptotic and cytotoxic effects of hesperidin and berberine in both nano form and combination. These findings indicate that berberine and hesperidin in combination, especially in nano form, hold significant promise as a treatment approach for prostate cancer.