title: Determination of in Vitro and in Silico Indexes for the Modeling of Blood-Brain Barrier Partitioning of Drugs via Micellar and Immobilized Artificial Membrane Liquid Chromatography.
abstract: In the present work, 79 structurally unrelated analytes were taken into account and their chromatographic retention coefficients, measured by immobilized artificial membrane liquid chromatography (IAM-LC) and by micellar liquid chromatography (MLC) employing sodium dodecyl sulfate (SDS) as surfactant, were determined. Such indexes, along with topological and physicochemical parameters calculated in silico, were subsequently used for the development of blood-brain barrier passage-predictive statistical models using partial least-squares (PLS) regression. Highly significant relationships were observed either using IAM (r2(n - 1) = 0.78) or MLC (r2(n - 1) = 0.83) derived indexes along with in silico descriptors. This hybrid approach proved fast and effective in the development of highly predictive BBB passage oriented models, and therefore, it can be of interest for pharmaceutical industries as a high-throughput BBB penetration oriented screening method. Finally, it shed new light into the molecular mechanism involved in the BBB uptake of therapeutics.
authors.affiliation: Separation Science Group, Department of Organic and Macromolecular Chemistry, Ghent University , Krijgslaan 281, S4-bis, B-9000 Gent, Belgium.|Dipartimento di Farmacia, Università degli Studi di Napoli Federico II , Via D. Montesano, 49, I-80131 Naples, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Russo
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Napoli Federico II , Via D. Montesano, 49, I-80131 Naples, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Grumetto
authors.affiliation: Pfizer Global R&D , Sandwich CT13 9NJ, Kent, United Kingdom.
authors.forename: Roman
authors.initials: R
authors.lastname: Szucs
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Napoli Federico II , Via D. Montesano, 49, I-80131 Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Barbato
authors.affiliation: Separation Science Group, Department of Organic and Macromolecular Chemistry, Ghent University , Krijgslaan 281, S4-bis, B-9000 Gent, Belgium.
authors.forename: Frederic
authors.identifier: 0000-0002-4690-7690
authors.initials: F
authors.lastname: Lynen
mesh_terms: D001812:Blood-Brain Barrier; D002853:Chromatography, Liquid / Q000379:methods*; D003198:Computer Simulation; D015195:Drug Design; D066298:In Vitro Techniques; D008567:Membranes, Artificial; D008823:Micelles; D008958:Models, Molecular; D008962:Models, Theoretical
chemical_list: D008567:Membranes, Artificial; D008823:Micelles