title: Surface activity profiling of drugs applied to the prediction of blood-brain barrier permeability.
abstract: The present study describes a novel in vitro platform for physicochemical profiling of compounds, based on their impact on the air/water interfacial tension. Interfacial partitioning coefficient, cross-sectional area, and critical micelle concentration were derived from the Gibbs adsorption isotherms recorded for 76 structurally diverse drugs. An approximation for the membrane partitioning coefficient, K(memb), is introduced and calculated for the measured compounds. This methodology provides a fully automatic, high-throughput screening technique for compound characterization, yielding precise thermodynamic information on the partitioning behavior of molecules at air/water interfaces, which can be directly related to their anisotropic interaction with lipid bilayers in biological membranes. The latter represents the barrier for the passive entry of compounds into cells. The surface activity profiles are shown to correlate to the ability of the compounds to pass passively through the blood-brain barrier.
authors.affiliation: Kibron Inc., P.O. Box 141, FIN-00171 Helsinki, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Suomalainen
authors.forename: Christoffer
authors.initials: C
authors.lastname: Johans
authors.forename: Tim
authors.initials: T
authors.lastname: Söderlund
authors.forename: Paavo K J
authors.initials: PK
authors.lastname: Kinnunen
mesh_terms: D001812:Blood-Brain Barrier / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry; D008823:Micelles; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D008051:Lipid Bilayers; D008823:Micelles; D004364:Pharmaceutical Preparations