title: Enhancement of carboplatin toxicity by Pluronic block copolymers.
abstract: The objective of this study was to examine the effects of three Pluronic triblock copolymers (F127, 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-Grünwald and Giemsa staining. Results indicate that the greatest enhancement of carboplatin toxicity was induced by P85, where the inhibitory concentration (IC(50)) 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.
authors.affiliation: Department of Radiology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106-5056, USA. Exner@uhrad.com
authors.forename: Agata A
authors.initials: AA
authors.lastname: Exner
authors.forename: Tianyi M
authors.initials: TM
authors.lastname: Krupka
authors.forename: Katherine
authors.initials: K
authors.lastname: Scherrer
authors.forename: J Maxwell
authors.initials: JM
authors.lastname: Teets
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004337:Drug Carriers; D008823:Micelles; D011060:Poloxalene / Q000008:administration & dosage*; D020442:Poloxamer / Q000008:administration & dosage*; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; C422648:pluronic block copolymer p85; C480965:pluronic L61; D020442:Poloxamer; D011060:Poloxalene; D016190:Carboplatin