Superoxide dismutase-loaded PLGA nanoparticles protect cultured human neurons under oxidative stress.
The objective of our study was to investigate the neuroprotective efficacy of superoxide dismutase (SOD), loaded in poly(D,L-lactide co-glycolide; PLGA) nanoparticles (NPs), in cultured human neurons challenged with hydrogen peroxide (H(2)O(2))-induced oxidative stress. We hypothesized that the protected and sustained intracellular delivery of SOD encapsulated in NPs would demonstrate better neuroprotection from oxidative stress than either SOD or pegylated SOD (PEG-SOD) in solution. SOD-NPs (approximately 81 +/- 4 nm in diameter, 0.9% w/w SOD loading) released the encapsulated SOD in an active form with 8.2% cumulative release during the first 24 h, followed by a slower release thereafter. The results demonstrated that PLGA-NPs are compatible with human neurons, and the neuroprotective effect of SOD-NPs is dose-dependent, with efficacy seen at >100 U SOD, and less significant effects at lower doses. Neither SOD (25-200 U) nor PEG-SOD (100 U) in solution demonstrated the neuroprotective effect under similar conditions. The neuroprotective effect of SOD-NPs was seen up to 6 h after H(2)O(2)-induced oxidative stress, but the effect diminished thereafter. Confocal microscopic studies demonstrated better intracellular neuronal uptake of the encapsulated model protein (fluorescein isothiocyanate-labeled BSA) than the protein in solution. Thus, the mechanism of efficacy of SOD-NPs appears to be due to the stability of the encapsulated enzyme and its better neuronal uptake after encapsulation.
Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Maram K
MK
Reddy
Li
L
Wu
Wei
W
Kou
Anuja
A
Ghorpade
Vinod
V
Labhasetwar
D000975:Antioxidants / Q000008:administration & dosage; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004795:Enzyme Stability; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D019344:Lactic Acid / Q000008:administration & dosage*; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013482:Superoxide Dismutase / Q000008:administration & dosage*
D000975:Antioxidants; D003692:Delayed-Action Preparations; D018696:Neuroprotective Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase