title: Docetaxel-loaded liposomes: preparation, pH sensitivity, pharmacokinetics, and tissue distribution.
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.
authors.affiliation: School of Pharmaceutical Science, Shandong University, Jinan 250012, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Rui-ying
authors.initials: RY
authors.lastname: Li
authors.forename: Xia
authors.initials: X
authors.lastname: Lu
authors.forename: Zhen-zhen
authors.initials: ZZ
authors.lastname: Mou
authors.forename: Gui-mei
authors.initials: GM
authors.lastname: Lin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D004058:Diffusion; D000077143:Docetaxel; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D043823:Taxoids / Q000737:chemistry* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D008081:Liposomes; D043823:Taxoids; D000077143:Docetaxel