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Poly(Ethylene Glycol)-based Crosslinked Networks with Potential Multidrug Resistance 1 (MDR1) Protein Inhibition Effects

Biomaterials and Biomedical Engineering Laboratory, Department of Chemical Engineering, University of Puerto Rico-Mayagüez Campus Mayagüez, Puerto Rico

Janet Méndez-Vega

Biomaterials and Biomedical Engineering Laboratory, Department of Chemical Engineering, University of Puerto Rico-Mayagüez Campus Mayagüez, Puerto Rico

Madeline Torres-Lugo

Biomaterials and Biomedical Engineering Laboratory, Department of Chemical Engineering, University of Puerto Rico-Mayagüez Campus Mayagüez, Puerto Rico, madeline{at}ece.uprm.edu

Linear poly(ethylene glycol) based structures have emerged as possible inhibitors for the multidrug resistance (MDR) proteins and recognized as a major hurdle during drug absorption and distribution. In this report, PEG-based hydrogels were evaluated for transport enhancement of the known MDR1 substrate Rhodamine 123. The expression of the MDR1 protein was corroborated using an immunostaining technique. The results indicated that these hydrogels are capable of enhancing the transport of Rhodamine 123 up to 350%, most likely due to MDR1 inhibition. The length of the PEG tethered chain appears to play an important role on transport enhancement as well the concentration of PEG hydrogel. This was taken as evidence of a possible inhibition effect of the MDR1 protein. When compared to the known inhibitors, genistein and verapamil, the PEG hydrogels provided similar efflux ratio, but the transport enhancement was lower. This is the first evidence of the role of crosslinked PEG-based hydrogels as possible inhibitors of the MDR1 protein.

Key Words: hydrogels • poly(ethylene glycol) • drug delivery • multidrug resistance proteins • MDR • PEG hydrogels.

Journal of Bioactive and Compatible Polymers, Vol. 24, No. 5, 444-456 (2009)
DOI: 10.1177/0883911509343495


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