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

• Published in: Journal of Zhejiang University. B. Science Vol. 13; no. 12; pp. 981 - 989
• Main Authors: Zhang, Hong, Li, Rui-ying, Lu, Xia, Mou, Zhen-zhen, Lin, Gui-mei
• Format: Journal Article
• Language: English
• Published: Heidelberg SP Zhejiang University Press 01.12.2012; Springer Nature B.V; Zhejiang University Press
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Biomedical and Life Sciences; Biomedicine; Biomedicine & Biotechnology; Delayed-Action Preparations - chemical synthesis; Delayed-Action Preparations - pharmacokinetics; Diffusion; Hydrogen-Ion Concentration; Liposomes - chemistry; Metabolic Clearance Rate; Mice; Organ Specificity; Taxoids - chemistry; Taxoids - pharmacokinetics; Tissue Distribution; 制剂学; 剂型; 药剂学; 调剂学; Tissue distribution; R944.9; Pharmacokinetics; pH sensitivity; Docetaxel-loaded liposomes
• ISSN: 1673-1581; 1862-1783; 1862-1783
• DOI: 10.1631/jzus.B1200098

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 zetapotential 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 releaseability of DTX-Lips. Pharmacokinetic and pharmaceutical studies in comparison with Duopafei showed that the half-timeperiod （t1/2） 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. The seresults together suggest that the DTX-Lips could be a promising formulation for the clinical administration of DTX.