Under development

Fluorosome®-trans-pgp: a rapid means to screen drug candidates
for interaction with a major drug-resistance efflux pump

An essential criterion for the success of a drug is its ability to reach its target site. Many potentially valuable drugs are ineffective because they do not reach their target sites in a sufficient concentration to be effective. A major reason for this is that many drugs cannot enter cells or cross the barriers that exist between the various compartments of the body (e.g. intestinal epithelial cells, blood-brain barrier, placenta) due to the action of energy driven efflux proteins, which actively pump a large variety of membrane soluble drugs away from their target tissue.

Due to the need for a simple assay to screen the susceptibility of drug candidates to the action of drug efflux pumps, we are developing the Fluorosome®-trans-pgp assay. This assay has the most important member of the family of drug efflux pumps, the p-glycoprotein (PGP, MDR1), incorporated into the membrane bilayers of the Fluorosome®-trans system.

Fluorosome®-trans are liposomal nano-particles developed by The Fluorosome Company to measure the passive diffusion rates of substances through true membrane lipid bilayers. Fluorosome®-trans-pgp will provide a convenient in vitro assay to screen the susceptibility of drug candidates for extrusion away from their target tissue and for PGP inhibitors. The Fluorosome®-trans-pgp assay will be applicable to a wide range of compound types and employ the FS-1, standard spectrofluorimeters, or fluorescent plate readers.

Fluorosome®-trans-pgp measures the susceptibility of a drug to efflux by the p-glycoprotein efflux pump. The equilibrium concentration of the drug within the fluorosome is indicated by the signal level of the emission beam. Measurements are made with the p-glycoprotein pump active (in the presence of ATP) and inactive (in the absence of ATP). The difference in the emission intensity in the presence and absence of ATP reflects the ability of the p-glycoprotein pump to efflux the drug.