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

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.

SUBMITTER: Zhang H

PROVIDER: S-EPMC4167557 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Zhang Hongyong H Li Yuanpei Y Lin Tzu-Yin TY Xiao Kai K Haddad Ashraf S AS Henderson Paul T PT Jonas Brian A BA Chen Mingyi M Xiao Wenwu W Liu Ruiwu R Lam Kit S KS Pan Chong-xian CX

Nanomedicine (London, England) 20140317 12

<h4>Background</h4>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.<h4>Materials & methods</h4>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 cre ...[more]

PMID: 24628688

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

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

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