Effect of charge ratio on lipoplex-mediated gene delivery and liver toxicity

Ther Deliv. 2015;6(11):1243-53. doi: 10.4155/tde.15.77. Epub 2015 Nov 26.

Abstract

Background: The vast majority of studies investigating gene delivery have utilized cationic delivery vehicles, but anionic nanoparticles can also possess high transfection activity, and offer significant benefits in terms of ease of preparation and reduced toxicity.

Results: Our study on lipoplexes possessing cholesterol nanodomains demonstrates that in vitro transfection after exposure to serum can be high at anionic charge ratios, and that this effect is also evident in studies assessing delivery to tumors in vivo, despite reduced circulation times. In addition, accumulation in the liver and lungs is reduced as compared with lipoplexes formulated at cationic charge ratios.

Conclusion: Lipoplexes prepared at anionic charge ratios offer comparable tumor delivery and reduced liver toxicity despite shorter circulation times.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Biological Availability
  • Cell Line, Tumor
  • Female
  • Humans
  • Ions / administration & dosage
  • Ions / adverse effects
  • Ions / blood
  • Liver / drug effects*
  • Liver / metabolism
  • Lung / metabolism
  • Mice
  • Nanoparticles / administration & dosage*
  • Nanoparticles / adverse effects*
  • Neoplasms / metabolism
  • Nucleic Acids / administration & dosage*
  • Nucleic Acids / blood
  • Nucleic Acids / pharmacokinetics*
  • Particle Size
  • Transfection / methods*

Substances

  • Ions
  • Nucleic Acids
  • Alanine Transaminase