Folate receptor-targeted PEGylated PLGA nanoparticles for the site-specific delivery of hesperidin in epithelial ovarian cancer.

Hesperidin (HSP) is a polyphenolic compound employed widely in the therapy of epithelial ovarian cancer (EOC). However, the low bioavailability, attributed to first-pass metabolism, low dissolution and poor tumour specificity, hampered its clinical effectiveness. Therefore, HSP-loaded folic acid-PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (HSP-PEGylated PLGA FA NPs) were synthesized to improve dissolution and target specificity of HSP for the management of EOC. The NPs were synthesized by nanoprecipitation and assessed for entrapment efficiency, particle size, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and in vitro dissolution. Additionally, antioxidant assay, cytotoxicity, cellular uptake and flow cytometric were performed on folate receptor overexpressing SKOV3 cell line. Physico-chemical characterization supported the formation of HSP-PEGylated PLGA FA NPs with entrapment efficiency ∼89.34%, particle size ∼205 nm, and a zeta potential of ∼ -25 mV, demonstrating their physical stability. The NPs enhanced HSP release at pH 5.5 compared to pH 7.4. The NPs showed greater cytotoxicity at an IC50 value of ∼29 µM/mL and enhanced early apoptosis ∼44% as compared to HSP-PEGylated PLGA NPs ∼32% towards the FA receptor overexpressed EOC cell line. The developed formulation shows promising potential as a targeted NP system for the management of EOC.