In vivo behavior of MIL-100 nanoparticles at early times after intravenous administration

Int J Pharm. 2016 Sep 25;511(2):1042-7. doi: 10.1016/j.ijpharm.2016.08.010. Epub 2016 Aug 8.

Abstract

Metal-organic frameworks have shown interesting features for biomedical applications, such as drug delivery and imaging agents. The benchmarked mesoporous iron(III) trimesate MIL-100 MOF nanocarrier combines progressive release of high drug cargoes with absence of visible in vivo toxicity. Although in a previous study pharmacokinetics and biodistribution of MIL-100 nanoparticles were evaluated in the long term (from 24h to 1 month), the crucial times for drug targeting and delivery applications are shorter (up to 24h). Thus, this work aims to study the blood circulating profile and organ accumulation of MIL-100 nanocarrier at early times after administration. For this purpose, after intravenous administration to rats, both constitutive components of MIL-100 (trimesate and iron) were quantified by high performance liquid chromatography and a spectrophotometric method, respectively. The pharmacokinetic profile suggested that the nanoparticles act as a depot in the blood stream during the first hours before being cleared. Accumulation took mainly place in the liver and, in some extent, in the spleen. Nevertheless, histological studies demonstrated the absence of morphological alterations due to the presence of the particles in these organs. Liver function was however slightly altered as reflected by the increased plasma aspartate aminotransferase concentrations. Finally trimesate was progressively eliminated in urine.

Keywords: Biodistribution; Coordination polymers; Drug delivery system pharmacokinetics; Iron (PubChem CID: 23925); Metal-organic frameworks; Trimesic acid (PubChem CID: 11138).

MeSH terms

  • Administration, Intravenous
  • Animals
  • Biological Availability
  • Female
  • Iron Compounds / administration & dosage*
  • Iron Compounds / metabolism*
  • Nanoparticles / administration & dosage*
  • Nanoparticles / metabolism*
  • Rats
  • Rats, Wistar
  • Time Factors

Substances

  • Iron Compounds