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Docetaxel-loaded liposomes: preparation, pH sensitivity, Pharmacokinetics, and tissue distribution

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Abstract

Docetaxel (DTX), as a member of taxoid family, has been widely used in the treatment of cancers. The present study prepared pH-sensitive DTX-loaded liposomes (DTX-Lips) by thin-film dispersion method and various physico-chemical and morphological properties were examined. The pH sensitivity of in vitro DTX release and the in vivo pharmacokinetics and tissue distribution using Kunming mice were also investigated. The mean particle size and zeta potential of DTX liposomes were (277±2) nm and (−32.60±0.26) mV, respectively. Additionally, in vitro drug release study showed that the cumulative release rate was 1.3 times more at pH 5.0 than at pH 7.4, suggesting a pH-dependent release ability of DTX-Lips. Pharmacokinetic and pharmaceutical studies in comparison with Duopafei® showed that the half-time period (t 1/2) and area under the curve (AUC) of DTX-Lips in mouse plasma were 1.8 times longer and 2.6 times higher, respectively, and that DTX-Lips selectively accumulated in macrophage-rich organs such as liver and spleen. These results together suggest that the DTX-Lips could be a promising formulation for the clinical administration of DTX.

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Authors and Affiliations

  1. School of Pharmaceutical Science, Shandong University, Jinan, 250012, China

    Hong Zhang, Rui-ying Li, Xia Lu, Zhen-zhen Mou & Gui-mei Lin

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  1. Hong Zhang
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  2. Rui-ying Li
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  3. Xia Lu
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  4. Zhen-zhen Mou
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  5. Gui-mei Lin
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Correspondence to Gui-mei Lin.

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Project supported by the Independent Innovation Foundation of Shandong University, China (No. 2010TS041) and the Shandong Provincial Special Funds for Postdoctoral Innovative Projects, China (No. 201003069)

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Zhang, H., Li, Ry., Lu, X. et al. Docetaxel-loaded liposomes: preparation, pH sensitivity, Pharmacokinetics, and tissue distribution. J. Zhejiang Univ. Sci. B 13, 981–989 (2012). https://doi.org/10.1631/jzus.B1200098

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  • DOI: https://doi.org/10.1631/jzus.B1200098

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