Toxicological evaluation of pH-sensitive nanoparticles of curcumin: acute, sub-acute and genotoxicity studies

Food Chem Toxicol. 2010 Aug-Sep;48(8-9):2073-89. doi: 10.1016/j.fct.2010.05.008. Epub 2010 May 12.

Abstract

Research in nanotoxicology is still in nascent stages. This hampers the design of appropriate regulatory policies for these beneficial nano-drug delivery systems thus affecting their routine employment as therapeutics. Establishing the entire toxicological profile is thus indispensable for proving the human safety of nanocarriers, which was the primary objective of the current investigation. The developed curcumin loaded polymeric nanoparticles of Eudragit S100 were subjected to various toxicological evaluations which included acute-toxicity study, sub-acute-toxicity study (28 days) and various genotoxicity studies like in vivo Micronucleus assay, in vivo Chromosomal Aberration assay and in vivo Comet assay. The formulation was found to be non-toxic at the dose equivalent to 2000 mg/kg of body weight of curcumin in the acute-toxicity study. Sub-acute-toxicity study proved the safety of the formulation for prolonged administration at the commonly used therapeutic dose of 100mg/kg of body weight of curcumin and at twice the therapeutic dose. Genotoxicity studies proved the cellular safety of the developed formulation at the therapeutic dose, and even at doses equivalent to thrice the therapeutic dose. Thus the developed curcumin loaded polymeric nanoparticles of Eudragit S100 were found to be safe for oral administration for a short as well as a prolonged duration.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Chromosome Aberrations / drug effects
  • Comet Assay
  • Curcumin / chemistry
  • Curcumin / toxicity*
  • Eating / drug effects
  • Female
  • Hydrogen-Ion Concentration
  • Male
  • Mice
  • Micronucleus Tests
  • Mutagenicity Tests
  • Mutagens / toxicity*
  • Nanoparticles / chemistry
  • Nanoparticles / toxicity
  • Organ Size / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Sex Characteristics

Substances

  • Mutagens
  • Curcumin