Nanomicelle formulation modifies the pharmacokinetic profiles and cardiac toxicity of daunorubicin

Hongyong Zhang, Yuanpei Li, Tzu Yin Lin, Kai Xiao, Ashraf S. Haddad, Paul T. Henderson, Brian A. Jonas, Mingyi Chen, Wenwu Xiao, Ruiwu Liu, Kit S. Lam, Chong Xian Pan

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background: Treatment with daunorubicin (DNR) in acute myeloid leukemia is moderately effective and associated with significant side effects, including cardiac toxicity. We recently developed a nanomicellar formulation of DNR that specifically targets acute myeloid leukemia stem cells. Materials & methods: Pharmacokinetics analysis of free DNR, DNR in nanomicellar formulations was performed in Balb/c mice and Sprague - Dawley rats. Histochemical staining, caspase 3/7, troponin and creatine kinase MB isoenzyme were used to assess toxicity. Results: Compared with free DNR, the nanomicellar formulations of DNR had less cardiotoxicity as evidenced by milder histopathological changes, lower caspase 3/7 activity in heart tissue (p = 0.002), lower plasma creatine kinase MB isoenzyme (p = 0.002) and troponin concentrations (p = 0.001) postinjection. The area under curve concentration of DNR in micelles increased by 31.9-fold in mice (p < 0.0001) and 22.0-fold higher in rats (p < 0.001). Conclusion: Leukemia stem cell-targeting micelles dramatically change the pharmacokinetics and reduce the cardiac toxicity of DNR, which may enable improved DNR-based treatment of acute myeloid leukemia.

Original languageEnglish (US)
Pages (from-to)1807-1820
Number of pages14
JournalNanomedicine
Volume9
Issue number12
DOIs
StatePublished - Aug 1 2014

Keywords

  • Cardiotoxicity
  • Daunorubicin
  • Leukemia stem cells
  • Nanomicelles
  • Pharmacokinetics

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)

Fingerprint Dive into the research topics of 'Nanomicelle formulation modifies the pharmacokinetic profiles and cardiac toxicity of daunorubicin'. Together they form a unique fingerprint.

Cite this