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Nanomicelle formulation modifies the pharmacokinetic profiles and cardiac toxicity of daunorubicin.

  • Author(s): Zhang, Hongyong
  • Li, Yuanpei
  • Lin, Tzu-Yin
  • Xiao, Kai
  • Haddad, Ashraf S
  • Henderson, Paul T
  • Jonas, Brian A
  • Chen, Mingyi
  • Xiao, Wenwu
  • Liu, Ruiwu
  • Lam, Kit S
  • Pan, Chong-xian
  • et al.

Published Web Location

https://doi.org/10.2217/nnm.14.44Creative Commons 'BY-NC-ND' version 4.0 license
Abstract

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.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.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).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.

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