A new colorimetric assay for studying and rapid screening of membrane penetration enhancers.
OBJECTIVE
This work aims to demonstrate a novel chemical assay for rapid screening and analysis of the mode of action of membrane interaction by penetration enhancers.


METHODS
The new bio-mimetic membrane assembly, consisting of supramolecular aggregates of lipids and conjugated polydiacetylene, undergoes visible and quantifiable blue-red color transitions upon interaction with penetration enhancers.


RESULTS
The new colorimetric model has been employed to examine various classes of penetration enhancers, including 1-dodecylhexahydro-2H-azepin-2-one (Azone), oleic acid, propylene-glycol, menthol, ethoxyglycol-diethyleneglycol-monoethyl-ether (Transcutol), polysorbate-polyethylenesorbitan-monolaurate (Tween-20), and the drug 7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one (Diazepam). The assay enables to evaluate the validity of various observations and hypotheses proposed in previous studies regarding permeation enhancement activities. Our results suggest, for example. that propylene glycol (PG) by itself does not interfere with membranes, but rather exhibits synergistic effect in combination with other penetration enhancers. Similarly, 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 rapid screening of the activities of penetration enhancers, and provides insight into the mechanisms of permeability of membrane-active compounds.
Evrard
D
D
Department of Chemistry and Stadler Minerva Center for Mesoscale Macromolecular Engineering, Ben Gurion University of the Negev, Beersheva, Israel.
Touitou
E
E
Kolusheva
S
S
Fishov
Y
Y
Jelinek
R
R
D000114:Acetylene / Q000031:analogs & derivatives* / Q000737:chemistry; D003124:Colorimetry / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008567:Membranes, Artificial; D010539:Permeability; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D000078789:Polyacetylene Polymer; D011108:Polymers / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D053279:Polyynes; D019946:Propylene Glycol / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D013501:Surface-Active Agents / Q000737:chemistry*
D008567:Membranes, Artificial; D014677:Pharmaceutical Vehicles; D010743:Phospholipids; D000078789:Polyacetylene Polymer; D011108:Polymers; D011136:Polysorbates; D013501:Surface-Active Agents; D053279:Polyynes; C082361:polydiacetylene; D019946:Propylene Glycol; D000114:Acetylene