Nanotechnology combined with eco-friendly refinement as an innovative drug delivery approach for Passiflora edulis f. flavicarpa – An antidepressant flavonoid-rich fraction loaded biocompatible nanoparticles

Flavonoids founded in Passiflora species are phenolics compounds with large neuropharmacological activity, but their physicochemical properties limit their pharmaceutical applications. In this sense, self-assembled polymeric nanoparticles were prepared by nanoencapsulation of a flavonoid-rich fraction (FRF) from leaves of P. edulis f. flavicarpa into Eudragit E PO polymethylmethacrylate copolymer by using solvent displacement method. FRF from P. edulis leaf extract was obtained by eco-friendly fractionation techniques and it exhibited high total flavonoid content (37.1%; 371.38 mg/g), and fifteen C and/or O -glycosyl flavones molecules were putative identified by LC-MS/MS. The addition of FRF at different weight percent loadings of nanoparticles was investigated. The morphology, physical-chemical properties, and stability of nanoparticles were characterized through size and zeta potential measurements, infrared spectroscopy (ATR-IFTR), atomic absorption microscopy (AFM), and efficiency entrapment by UHPLC-UV-DAD. Assessment of in vivo biocompatibility and antidepressant-like activity and effects on spontaneous locomotion investigated in mice. The developed FRF nanoparticles exhibited good small-sized and spherical, high content and encapsulation efficiency of bioactive flavonoids, good biocompatibility and increased the antidepressant efficacy (10-fold) compared to free FRF. The small size and positive charge make these nanoparticles containing FRF a potential Active Pharmaceutical Ingredient for targeting neuroactive flavonoids to the central nervous system.