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Examination of the mechanisms of Interaction of PEG-rich Matrices with the MRP and MDR Transporters

Abstract

The multidrug resistance protein (MRP) and the p-glycoproteins are apical polarized transporters that have been related to the development of drug resistance to chemotherapeutic agents used for cancer treatment. Linear polymers containing poly(ethylene glycol) on their structures have been identified to affect the transport of MRP and p-glycoprotein substrates by unknown mechanisms.

This project envisions the understanding of the physicochemical interactions of poly(ethylene glycol) rich matrices with the multidrug resistance protein (MRP) and the p-glycoprotein.

To achieve this goal, transport experiments of various MRP and MDR fluorescent substrates will be carried out utilizing the Caco-2 cell line. These experiments will be performed in the presence and absence of PEG-rich matrices that will be specifically designed and tailored. Specific MRP and MDR inhibitors will be employed as secondary controls. This information will provide the optimal concentration and molecular weight of poly(ethylene glycol) chains in the polymeric matrix.




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