A new colorimetric assay for studying and rapid screening of membrane penetration enhancers

Purpose. This work aims to demonstrate a novel chemical assay for rapid scr eening and analysis of the mode of action of membrane interaction by penetr ation enhancers. Methods. The new bio-mimetic membrane assembly, consisting of supramolecula r aggregates of lipids and conjugated polydiacetylene, undergoes visible an d quantifiable blue-red color transitions upon interaction with penetration enhancers. Results. The new colorimetric model has been employed to examine various cl asses of penetration enhancers, including 1-dodecylhexahydro-2H-azepin-2-on e (Azone). oleic acid, propylene-glycol, menthol, ethoxyglycol-diethylenegl ycol-monoethyl-ether (Transcutol), polysorbate-polyethylenesorbitan-monolau rate (Tween-20), and the drug 7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazep in-2-one (Diazepam). The assay enables to evaluate the validity of various observations and hypotheses proposed in previous studies regarding permeati on enhancement activities. Our results suggest, for example, that propylene glycol (PG) by itself does not interfere with membranes, but rather exhibi ts synergistic effect in combination with other penetration enhancers. Simi larly, our data demonstrate that Transcutol does not independently interact with membranes. The colorimetric system also indicates that interaction of penetration enhancers with membranes depend upon the lipid phase, as well as the self-assembly properties of the enhancer molecules. Conclusions. The new biomimetic model membrane system can be applied for ra pid screening of the activities of penetration enhancers, and provides insi ght into the mechanisms of permeability of membrane-active compounds.