A new approach to reduce toxicities and to improve bioavailabilities of platinum-containing anti-cancer nanodrugs

Sci Rep. 2015 Jun 3:5:10881. doi: 10.1038/srep10881.

Abstract

Platinum (Pt) drugs are the most potent and commonly used anti-cancer chemotherapeutics. Nanoformulation of Pt drugs has the potential to improve the delivery to tumors and reduce toxic side effects. A major challenge for translating nanodrugs to clinical settings is their rapid clearance by the reticuloendothelial system (RES), hence increasing toxicities on off-target organs and reducing efficacy. We are reporting that an FDA approved parenteral nutrition source, Intralipid 20%, can help this problem. A dichloro (1, 2-diaminocyclohexane) platinum (II)-loaded and hyaluronic acid polymer-coated nanoparticle (DACHPt/HANP) is used in this study. A single dose of Intralipid (2 g/kg, clinical dosage) is administrated [intravenously (i. v.), clinical route] one hour before i.v. injection of DACHPt/HANP. This treatment can significantly reduce the toxicities of DACHPt/HANP in liver, spleen, and, interestingly, kidney. Intralipid can decrease Pt accumulation in the liver, spleen, and kidney by 20.4%, 42.5%, and 31.2% at 24-hr post nanodrug administration, respectively. The bioavailability of DACHPt/HANP increases by 18.7% and 9.4% during the first 5 and 24 hr, respectively.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / toxicity*
  • Biological Availability
  • Chemistry, Pharmaceutical
  • Hyaluronic Acid / chemistry
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Nanoparticles* / chemistry
  • Platinum / pharmacokinetics*
  • Platinum / toxicity*
  • Polymers / chemistry
  • Rats
  • Spleen / drug effects
  • Spleen / metabolism
  • Spleen / pathology
  • Theranostic Nanomedicine*

Substances

  • Antineoplastic Agents
  • Polymers
  • Platinum
  • Hyaluronic Acid