Triton-X-100-modified polymer and microspheres for reversal of multidrug resistance.
Triton X-100 is a non-ionic detergent capable of reversing multidrug resistance (MDR) due to its interaction with cell membranes. However, it interacts with cells in a non-specific way, causing cytotoxicity. This work aimed to develop polymeric chemosensitizers that possess the ability to reverse MDR and lower toxic side effects. When being delivered to tumours, the polymeric chemosensitizers may also have longer retention times in tumours than the free detergent. Triton-X-100-immobilized dextran microspheres (T-MS) and inulin (T-IN) were prepared and characterized. Their cytotoxicity against multidrug-resistant Chinese hamster ovary cells (CH(R)C5) was compared with that of free Triton X-100 solutions. The in-vitro effect of the products on 3H-vinblastine accumulation by CH(R)C5 cells was determined. Both T-MS and T-IN showed a marked decrease in the cytotoxicity, as compared with free Triton solutions at equivalent concentrations. Drug accumulation by CH(R)C5 cells was increased over two fold in the presence of T-MS or T-IN. These results suggest that polymeric drug carriers with MDR-reversing capability and lower cytotoxicity may be prepared by immobilization of chemosensitizers.
Liu
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Faculty of Pharmacy, University of Toronto, ON, Canada.
Bendayan
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R
Wu
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D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D016466:CHO Cells / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology*; D006224:Cricetinae; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D004354:Drug Screening Assays, Antitumor; D008863:Microspheres; D017830:Octoxynol / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry*; D013501:Surface-Active Agents / Q000494:pharmacology*; D014747:Vinblastine / Q000493:pharmacokinetics*
D000972:Antineoplastic Agents, Phytogenic; D011108:Polymers; D013501:Surface-Active Agents; D014747:Vinblastine; D017830:Octoxynol