Superoxide dismutase-loaded PLGA nanoparticles protect cultured human neurons under oxidative stress

Maram K. Reddy, Li Wu, Wei Kou, Anuja Ghorpade, Vinod Labhasetwar

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

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 (H2O2)-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 (~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 H2O2-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.

Original languageEnglish
Pages (from-to)565-577
Number of pages13
JournalApplied Biochemistry and Biotechnology
Volume151
Issue number2-3
DOIs
StatePublished - Dec 2008

Keywords

  • Antioxidant enzymes
  • Drug delivery
  • Free radicals
  • Polymers
  • Sustained release

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