The Cytotoxicity of Titanocene Y Against CAKI-1 Cells: An In Vitro Formulation Study

作者：Hogan Megan; Gleeson Brendan; Tacke Matthias^*

来源：Letters in Drug Design and Discovery, 2010, 7(5): 310-317.

DOI：10.2174/157018010791163479

• Titanocene Y
• Formulation
• CAKI-1 cells
• Cremophor EL
• Tween 80
• PEG-400
• Solutol HS 15
• Soluphor P
• Solubility
• Cytotoxicity
• MTT assay

Various formulations containing titanocene Y (bis-[(p-methoxybenzyl) cyclopentadienyl] titanium (IV) dichloride) were prepared and tested in vitro on CAKI-1 cells in order to compare the cytotoxic behaviour of the compound with different formulation reagents. Formulations were prepared with non-ionic surfactants like Cremophor EL and Tween 80, pegylated reagents PEG-400 and Solutol HS 15, and the co-solvent Soluphor P (pyrrolidone-2). All formulations were tested with and without the presence of dimethylsulfoxide. When the lipophilic derivative titanocene Y was formulated with Soluphor P and tested in vitro, an IC50 value of 10 (+/-1) mu M was observed, which is a 3-fold increase in cytotoxicity when compared to the DMSO formulation. In order to compare to a more hydrophilic titanocene this Soluphor P formulation method was extended to the water-soluble titanocene G, which is a dihydrochloride derivative of bis-[(1-methyl-3- dimethylaminomethylindol-2-yl) cyclopentadienyl] titanium (IV) dichloride). When titanocene G was tested in vitro in the presence of Soluphor P, it resulted in a 10-fold increase in cytotoxicity with an IC50 value of 0.71 (+/-0.24) mu M against CAKI-1 cells.

• 出版日期2010-6