期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 360, 期 1-2, 页码 115-121出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2008.04.027
关键词
chlorambucil; parenteral emulsion; pharmacokinetics; tissue distribution; anticancer activity; colon-38 adenocarcinoma
资金
- UniServices Drug Delivery Grant, The University of Auckland, New Zealand
The aim was to assess the pharmacokinetics and anticancer activity of chlorambucil (CHL) incorporated in a parenteral emulsion (PE). A chlorambucil-loaded PE was prepared by a high energy ultrasonication method. Soybean oil was chosen as a triglyceride oil core and egg phosphatidy1choline as an emulsifier in the formulation. The particle size distribution and zeta potential were measured using Zetasizer. The results showed that the average encapsulation efficiency of chlorambucil-loaded parenteral emulsion (CHL-PE) was 98.6 3.2% with a particle size of 182.7 0.8 nm, and a zeta-potential of -37.2 1.1 mV. Osmolality and pH of the formulation were 305.6 2.3 mOsm/kg and 7.4, respectively. The chlorambucil was stable in the PE for at least 6 months stored at 4-81C. The pharmacokinetics, tissue distribution, and anticancer activity of CHL-PE and chlorambucil solution were studied after intravenous administration to C57 BL/6 male mice. CHL-PE exhibited a significantly greater AUCO-_ (32.4 0.1 I.Lg/ml h vs. 16.9 0.1 l.Lg/mI h), mean residence time (MRT) (1.32 0.01 h vs. 0.30 0.01 h), volume of distribution (409 15 ml/kg vs. 180 7 ml/kg) and elimination half-life (1.83 0.1 h vs. 0.27 0.02 h) (all P< 0.01), and a significantly reduced plasma clearance (309 16 ml/(h kg) vs. 591 4 ml/(h kg), P< 0.01) compared to the CHL. In addition CHL-PE treatment caused significantly greater tumour growth suppression rate (%T/C) ofthe colon-38 adenocarcinoma in the mouse compared to CHL treatment (% T/C, 75 3.4% vs. 49 7.4%, P<0.01). These results suggest that CHL-PE could be an effective parenteral carrier for chlorambucil delivery in cancer treatment. 0 2008 Elsevier B.V. All rights reserved.
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