Role of a novel (-)-epigallocatechin-3-gallate delivery system on the prevention against oxidative stress damage in vitro and in vivo model of Parkinson's disease

Epigallocatechin-3-gallate (EGCG) is an antioxidant molecule that is studied, in this work, to evaluate its attenuating effect of the oxidative stress (OS) damage involved with the Parkinson disease (PD). To optimize the EGCG antioxidant effect, an appropriate deliver system is proposed that protects its stability and bioactivity and allows having a controlled delivery at the level of concentration required for obtaining such effect. The preparation of the novel core shell nanoparticles system for EGCG delivery starts from the formation of mixed micelles of the triblock copolymer Pluronic (R) F127 and sodium dodecyl sulfate surfactant followed by covering with chitosan and in situ EGCG encapsulation. The nanoparticles, after being purified by ultrafiltration, with average size around 35 nm, with encapsulation efficiency (%EE) of EGCG (similar to 83%) and exhibiting colloidal stability and an in vitro EGCG sustained release, were chosen to evaluate the antioxidant effects of EGCG in vitro on nerve-like cells (NLCs) and in vivo in OS model of PD. They protected NLCs against OS generated by rotenone (ROT) by reducing levels of H2O2, and oxidation of DJ-1 protein. They also maintained the mitochondrial membrane potential (Delta psi m) and reduced the activation of cell death markers (CASPASE 3). In in vivo studies these nanoparticles prevented to the knockdown parkin Drosophila melanogaster, exposed to paraquat, against induced locomotor impairment, lipid peroxidation, and life span diminution. This study reaffirms the beneficial use of EGCG as an antioxidant agent and shows, through in vivo OS model of PD, the importance of its controlled delivery from an appropriate system to attain optimum results.