Nanomicelle formulation modifies the pharmacokinetic profiles and cardiac toxicity of daunorubicin

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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

Fingerprint

Daunorubicin
Pharmacokinetics
Isoenzymes
Toxicity
toxicity
Stem cells
Micelles
Rats
fold
Acute Myeloid Leukemia
Caspase 7
MB Form Creatine Kinase
Troponin
Tissue
targeting
Plasmas
Caspase 3
stem
plasma
Myeloid Progenitor Cells

Keywords

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

ASJC Scopus subject areas

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

Cite this

Nanomicelle formulation modifies the pharmacokinetic profiles and cardiac toxicity of daunorubicin. / Zhang, Hongyong; Li, Yuanpei; Lin, Tzu-Yin; Xiao, Kai; Haddad, Ashraf S.; Henderson, Paul; Jonas, Brian; Chen, Mingyi; Xiao, Wenwu; Liu, Ruiwu; Lam, Kit; Pan, Chong-Xian.

In: Nanomedicine, Vol. 9, No. 12, 01.08.2014, p. 1807-1820.

Research output: Contribution to journalArticle

Zhang, Hongyong ; Li, Yuanpei ; Lin, Tzu-Yin ; Xiao, Kai ; Haddad, Ashraf S. ; Henderson, Paul ; Jonas, Brian ; Chen, Mingyi ; Xiao, Wenwu ; Liu, Ruiwu ; Lam, Kit ; Pan, Chong-Xian. / Nanomicelle formulation modifies the pharmacokinetic profiles and cardiac toxicity of daunorubicin. In: Nanomedicine. 2014 ; Vol. 9, No. 12. pp. 1807-1820.
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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.",
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AU - Henderson, Paul

AU - Jonas, Brian

AU - Chen, Mingyi

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AB - 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.

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