Subchronic and chronic toxicity evaluation of inorganic nanoparticles for delivery applications

Adv Drug Deliv Rev. 2019 Apr;144:112-132. doi: 10.1016/j.addr.2019.07.006. Epub 2019 Jul 8.


Inorganic nanoparticles provide the opportunity to localize bioactive agents to the target sites and protect them from degradation. In many cases, acute toxicities of inorganic nanoparticles used for delivery applications have been investigated. However, little information is available regarding the long-term toxicity of such materials. This review focuses on the importance of subchronic and chronic toxicity assessment of inorganic nanoparticles investigated for delivery applications. We have attempted to provide a comprehensive review of the available literature for chronic toxicity assessment of inorganic nanoparticles. Where possible correlations are made between particle composition, physiochemical properties, duration, frequency and route of administration, as well as the sex of animals, with tissue and blood toxicity, immunotoxicity and genotoxicity. A critical gap analysis is provided and important factors that need to be considered for long-term toxicology of inorganic nanoparticles are discussed.

Keywords: Drug delivery; Genotoxicity; Immunotoxicity; Long-term exposure; Nanoparticles; Nanotoxicology; Physiochemical properties; Route of administration; Tissue toxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Delivery Systems
  • Humans
  • Nanoparticles / toxicity*
  • Toxicity Tests, Chronic
  • Toxicity Tests, Subchronic