A rapid empirical method for measuring membrane bilayer entry equilibration of molecules

The therapeutic potency of many drugs is limited by their interactions with cell membranes. The ability of a drug to cross lipid barriers, such as those of cell membranes and the blood-brain barrier, to reach its site of action can be the determining factor in the effectiveness of a drug. In this paper we demonstrate the utility of fluorescently labeled liposomes, Fluorosomes, to measure the rate of penetration of small molecules into membrane lipid bilayers. This technique can be used to determine the half-times of bilayer entry equilibration of drugs of from milliseconds to hours for a wide variety of compound types at micromolar drug concentrations. This in vitro technique for measuring the nonprotein facilitated entry of drugs into the lipid phase of the membrane is suitable for the high-throughput screening of drugs.