In vitro cytotoxicity of paclitaxel/β-cyclodextrin complexes for HIPEC

被引:28
作者
Bouquet, W. [1 ]
Boterberg, T. [2 ]
Ceelen, W. [3 ]
Pattyn, P. [3 ]
Peeters, M. [4 ]
Bracke, M. [2 ]
Remon, J. P. [1 ]
Vervaet, C. [1 ]
机构
[1] Univ Ghent, Pharmaceut Technol Lab, B-9000 Ghent, Belgium
[2] Univ Ghent, Expt Cancerol Lab, B-9000 Ghent, Belgium
[3] Ghent Univ Hosp, Dept Abdominal Surg 0K12C, B-9000 Ghent, Belgium
[4] Ghent Univ Hosp, Dept Gastroenterol 1K12E, B-9000 Ghent, Belgium
关键词
Paclitaxel; Hyperthermic intraperitoneal chemotherapy (HIPEC); Cytotoxicity; MTT; SRB; beta-Cyclodextrin; HYPERTHERMIC PERITONEAL PERFUSION; TUMOR-NECROSIS-FACTOR; CREMOPHOR-EL; CELL-LINES; RAT MODEL; CANCER; ENHANCEMENT; TAXOL(R); PHARMACOKINETICS; CARCINOMATOSIS;
D O I
10.1016/j.ijpharm.2008.09.035
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising strategy in the treatment of peritoneal carcinomatosis. To perform HIPEC, a tensioactive- and solvent-free paclitaxel formulation consisting of water-soluble paclitaxel/randomly methylated-beta-cyclodextrin (Pac/RAMEB) complexes was developed previously. Using MTT and SRB assays the cytotoxic activity of this formulation versus Taxol (R). was evaluated as well as the cytotoxicity of the different formulation excipients (RAMEB and Cremophor EL (R)). The possible synergistic effect of heat and paclitaxel-based chemotherapy during HIPEC was also evaluated in vitro. The cytotoxicity assays revealed differences in viability between Cremophor EL (R) and RAMEB treated cells of 40 and 50% for the CaCo-2 human and the CC531s rat colon cancer line, respectively, in favour of RAMEB. Despite the higher cytotoxicity of Cremophor EL (R), Pac/RAMEB complexes and Taxol (R) were equipotent. Using the MTT and SRB assays the average difference in viability between both cell lines was below 10% and IC50 values showed no significant difference. Hyperthermia after drug administration (41 degrees C during 1 h) had no effect on cell viability. These results indicated that it was possible to reformulate paclitaxel with a less cytotoxic vehicle while maintaining the cytotoxic activity of the formulation and that there is no synergism between paclitaxel and heat for in vitro cytotoxicity. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:148 / 154
页数:7
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