Enhancement of carboplatin toxicity by Pluronic block copolymers

The objective of this study was to examine the effects of three Pluronic triblock copolymers (17127, P85, or L61) on the cytotoxicity of carboplatin to the DHB/K12/TRb rat colorectal carcinoma cell line. Studies to determine the dependence of the sensitization effect on Pluronic dose were carried out for polymer concentrations ranging from 0.0001-10% (w/w). To establish the carboplatin toxicity and its potential enhancement by Pluronic, the drug was delivered to cells in doses ranging from 0-0.5% (w/w) in the presence of Pluronic at a constant concentration. These treatment groups were compared to control groups receiving carboplatin alone. Cell cytotoxicity resulting from the treatments was determined with a mitochondrial enzyme activity assay (WST-1), while cell morphology was examined with May-Grunwald and Giemsa staining. Results indicate that the greatest enhancement of carboplatin toxicity was induced by P85, where the inhibitory concentration (IC50) was reduced by 50% (from 0.096 mg/mL for carboplatin alone to 0.048 mg/mL in presence of P85). L61 was toxic to the cells with or without drug (viability < 3.5%), while F127 exhibited no sensitizing effect and in some cases increased the cell viability to 130% over the untreated control. The WST-1 results were confirmed by trypan blue exclusion cell counts at 0 and 24 h post treatment. Data conclusively demonstrate that Pluronic P85 is the optimal agent for increased cytotoxicity of carboplatin in this cell line and can potentially be used not only as a drug delivery scheme but also as a chemosensitizing agent in future cancer therapy. (c) 2005 Elsevier B.V. All rights reserved.