Improved antioxidant effect of idebenone-loaded polyethyl-2-cyanoacrylate nanocapsules tested on human fibroblasts

Pharm Res. 2002 Jan;19(1):71-8. doi: 10.1023/a:1013659516878.

Abstract

Purpose: The protective antioxidant role of idebenone both as free drug and drug-loaded Tween 80-coated polyethyl-2-cyanoacrylate (PECA) nanocapsules is reported. The relationship between oxidative damage and apoptotic or nonapoptotic cell death is evaluated in vitro.

Methods: Idebenone-loaded nanocapsules were prepared with the interfacial polymerization method in the presence of Tween 80. Human nonimmortalized fibroblasts. under different stress conditions, either 0.5 mM diethylmaleate (DEM) for 60 min or 0.1 mM H2O2 for 30 min, were used as the experimental in vitro model. The production of reactive oxygen species, the cell viability, and the nuclear DNA damage were evaluated. The presence of apoptotic damage was evaluated both by the determination of caspase-3-like protein activity and by Promega's fluorescent apoptotic detection system.

Results: DEM and H2O2 affected the cultured cells in different ways. DEM induced a moderate cellular insult, which was efficaciously antagonized by idebenone-loaded PECA nanocapsules. H2O2 elicited severe damage to nuclear DNA, which was reduced by idebenoneloaded PECA nanocapsules. The free drug was less effective than idebenone-loaded nanocapsules.

Conclusions: The findings reported here demonstrate that an improved antioxidant effect was obtained with a low idebenone concentration (0.5 microM) when the drug was entrapped within Tween 80-coated PECA nanocapsules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Benzoquinones / pharmacology*
  • Capsules
  • Caspase 3
  • Caspases / metabolism
  • Cell Survival / drug effects
  • Cyanoacrylates / pharmacology*
  • DNA Damage / drug effects
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Fibroblasts / enzymology
  • Free Radical Scavengers / pharmacology*
  • Humans
  • Hydrogen Peroxide / toxicity
  • L-Lactate Dehydrogenase / metabolism
  • Maleates / toxicity
  • Oxidative Stress
  • Ubiquinone / analogs & derivatives

Substances

  • Antioxidants
  • Benzoquinones
  • Capsules
  • Cyanoacrylates
  • Free Radical Scavengers
  • Maleates
  • Ubiquinone
  • cyacrin
  • Hydrogen Peroxide
  • L-Lactate Dehydrogenase
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • diethyl maleate
  • idebenone