Targeted delivery of resveratrol using PEGylated PLGA nanoparticles decorated with folic acid for cancer therapy: characterization, and in vitro studies.

OBJECTIVE

This study aimed to develop, characterize, and evaluate resveratrol-loaded pegylated PLGA [poly (lactic-co-glycolic acid)] nanoparticles with folate conjugation for improved drug delivery and cytotoxic efficacy against MCF7 breast cancer cells.

SIGNIFICANCE: The significance of this drug delivery system is to enhance the wetting characteristics of resveratrol and reduce nanoparticle agglomeration for maximizing therapeutic efficacy while minimizing systemic cytotoxicity using PLGA and polyethylene glycol (PEG) polymeric nanoparticles as carriers. The process of fabrication and characterization of polymeric conjugate by utilizing PLGA-PEG surface engineered with folic acid for target specificity has already been investigated.

METHODS

Nanoparticles were prepared by double-emulsion solvent evaporation using PPF (PLGA-PEG-FOLATE conjugate polymer) and PVA (Poly vinyl alcohol) as a stabilizer. Compatibility studies were performed using FTIR, DSC, and XRD. Formulations (NF1-NF8) were evaluated for particle size, zeta potential, drug loading, entrapment efficiency, and in vitro release. Surface morphology was assessed by SEM and TEM. MTT assay evaluated cytotoxicity while fluorescence microscopy analyzed cellular uptake.

RESULTS

Compatibility studies confirmed no drug-excipient interactions. NF3 exhibited optimal characteristics: particle size 332.1 nm, zeta potential -24.6 mV, entrapment efficiency 78.65 ± 0.165%, and drug loading 36.19 ± 0.154%. In vitro release was sustained up to 120 h (75.17 ± 0.22%), fitting zero-order kinetics with Fickian diffusion. NF3 displayed enhanced cytotoxicity (IC50 340.26 nM) compared to free resveratrol (993.29 nM). Fluorescence microscopy confirmed improved cellular uptake via folate conjugation.

CONCLUSION

Resveratrol-loaded PPF nanoparticles, particularly NF3, demonstrated superior stability, sustained release, and enhanced anticancer activity, making them a promising candidate for targeted breast cancer therapy.