NANOPARTICLES-MEDIATED CATALASE DELIVERY PROTECTS HUMAN NEURONS FROM OXIDATIVE STRESS

Purpose: Several brain injuries and neurodegenerative diseases implicate excessive production of reactive oxygen species, such as hydrogen peroxide (H2O2) in disease pathogenesis. Catalase, an H2O2 degrading enzyme, is a well-known antioxidant target for therapeutic intervention. However, medical use of catalase is restricted by its labile nature and inadequate delivery to central nervous system. Methods: Here, a nanotechnology approach was evaluated that utilizes catalase-loaded, poly(lactic-co-glycolic acid) nanoparticles (NPs) to deliver catalase in order to protect human neurons from oxidative damage. Results: This study shows highly efficient catalase encapsulation capable of retaining ~ 99% enzymatic activity. NPs released catalase rapidly and antioxidant activity was sustained for over a month. Human neurons took up NPs rapidly and without toxicity. While human neurons are highly sensitive to H2O2, nanoparticle-mediated catalase delivery protected neuronal cultures from H2O2-induced oxidative stress. Catalase-loaded NPs significantly reduced H2O2-induced protein oxidation, DNA damage, mitochondrial membrane transition pore opening, loss of cell membrane integrity and restored cell morphology, neurite network and microtubule-associated protein-2 expression in neuronal cultures. Further, catalase-loaded NPs showed better neuronal recovery from H2O2 pre-exposure than non-encapsulated catalase enzyme, suggesting possible applications in ameliorating stroke relevant oxidative stress. Conclusions: Brain targeting of catalase-loaded NPs may find wide therapeutic applications for oxidative stress-associated acute and chronic neurodegenerative disorders.