Magnetic nanogels as dual triggered anticancer drug delivery: Toxicity evaluation on isolated rat liver mitochondria

Toxicol Lett. 2017 Aug 15:278:18-29. doi: 10.1016/j.toxlet.2017.06.004. Epub 2017 Jun 19.

Abstract

This study aimed to evaluate bio-safety of magnetic chitosan nanogels as dual triggered drug carrier for doxorubicin through analysis of mitochondrial function. In the present study, chitosan/TPP nanogels containing magnetite nanoparticles (NPs) were prepared according to the ionotropic gelation method as novel pH-sensitive magnetic nanogels. The NPs showed outstanding entrapment efficiency for doxorubicin (76.6%) with a sustained and high extent of drug release in the acidic media (pH=5-7) compared to the neutral media. Various mitochondrial functional parameters including complex II activity, MDA amount, GSH level, membrane potential collapse, swelling, apoptosis and release of cytochrome c were used to investigate the bio-safety of the nanogels. The findings revealed that the extent of mitochondrial dysfunction of doxorubicin were in the order of free doxorubicin>doxorubicin loaded magnetic nanogels=>doxorubicin loaded Nanogels. The results also revealed that the nanogels and the magnetite nanogels seem to possess promising capability as a safe carrier in comparison of the toxic potential effect of free doxorubicin.

Keywords: Bio-safety; Drug delivery; MTT assay; Magnetic nanogels; Mitochondrial dysfunction; Mitochondrial membrane potential (MMP) collapse.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity*
  • Apoptosis / drug effects
  • Chitosan / chemistry
  • Chitosan / toxicity*
  • Cytochromes c / metabolism
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry
  • Doxorubicin / toxicity*
  • Drug Carriers*
  • Drug Compounding
  • Drug Liberation
  • Glutathione / metabolism
  • Kinetics
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Magnetics / methods*
  • Magnetite Nanoparticles / chemistry
  • Magnetite Nanoparticles / toxicity*
  • Malondialdehyde / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Microscopy, Electron, Scanning
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / metabolism
  • Mitochondria, Liver / pathology
  • Mitochondrial Swelling / drug effects
  • Nanomedicine / methods*
  • Risk Assessment
  • Solubility
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared
  • Succinate Dehydrogenase / metabolism
  • Thermogravimetry

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Magnetite Nanoparticles
  • Malondialdehyde
  • Doxorubicin
  • Cytochromes c
  • Chitosan
  • Succinate Dehydrogenase
  • Glutathione