Synthesis and Characterization of Vincristine and ε‑Viniferin-Loaded Folate-Conjugated PLGA-PEG Nanoparticles and...

Recent studies highlight the potential of nanoparticles to enhance in vivo drug efficacy. Polylactide-co-glycolide acid (PLGA) is widely used for nanoparticle fabrication due to its biocompatibility, and PEGylation further improves its circulation time by reducing rapid reticuloendothelial system (RES) clearance. Folate-modified nanoparticles can additionally enable active targeting, as many cancer cells overexpress folate receptors. In this study, dual-drug-loaded and folate-targeted PLGA-polyethylene glycol (PEG) nanoparticles were developed, and their enhancing effects on cellular uptake, cytotoxicity, and apoptotic response were evaluated. The nanoparticles were prepared via the nanoprecipitation method. They exhibited a particle size of 276 ± 6 nm, a polydispersity index (PDI) of 0.5 ± 0.02, and a ζ potential of -19 ± 2 mV. The drug-loading capacity was 8.8% for ε-viniferine (EV) and 2.6% for vincristine sulfate (VS). The use of EV-VS-loaded PLGA-PEG-folate nanoparticles enhanced cytotoxicity and apoptosis compared to the free drug, reducing HepG2 cell viability from 94.3 to 53% at 10 μM EV + 1.64 μM VS and increasing early apoptotic cells from 15.3 to 31%, indicating their potential as a targeted drug delivery system for cancer cells.