Multilamellar liposomes and solid-supported lipid membranes (TRANSIL): Screening of lipid-water partitioning toward a high-throughput scale

Lipid-water partitioning of 187 pharmaceuticals has been assessed with solid-supported lipid membranes (TRANSIL) in microwell plates and with multilamellar liposomes for a data comparison. The high-throughput potential of the new approach was evaluated. Drugs were incubated at pH 7.4 with egg yolk l...

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Bibliographic Details
Published in:Pharmaceutical research 2001-12, Vol.18 (12), p.1782-1788
Main Authors: LOIDL-STAHLHOFEN, Angelika, HARTMANN, Thorsten, SCHÖTTNER, Matthias, RÖHRING, Cornelia, BRODOWSKY, Hanna, SCHMITT, Johannes, KELDENICH, Jörg
Format: Article
Language:English
Subjects:
Automation
Biological and medical sciences
Chromatography
Chromatography, High Pressure Liquid
General pharmacology
Investigations
Lipid Bilayers - chemistry
Lipids
Liposomes
Medical sciences
Membranes
Membranes, Artificial
Methods
Models, Biological
Optimization
Pharmaceutical Preparations - chemistry
Pharmaceutical technology. Pharmaceutical industry
Pharmaceuticals
Pharmacology. Drug treatments
Quantitative Structure-Activity Relationship
Water
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Summary:Lipid-water partitioning of 187 pharmaceuticals has been assessed with solid-supported lipid membranes (TRANSIL) in microwell plates and with multilamellar liposomes for a data comparison. The high-throughput potential of the new approach was evaluated. Drugs were incubated at pH 7.4 with egg yolk lecithin membranes either on a solid support (TRANSIL beads) or in the form of multilamellar liposomes. Phase separation of lipid and water phase was achieved by ultracentrifugation in case of liposomes or by a short filtration step in case of solid-supported lipid membranes. Lipid-water partitioning data of both approaches correlate well without systematic deviations in the investigated lipophilicity range. The solid-supported lipid membrane approach provides high-precision data in an automated microwell-plate setup. The lipid composition of the solid-supported lipid membranes was varied to study the influence of membrane change on lipid-water partitioning. In addition, pH-dependent measurements have been performed with minimal experimental effort. Solid-supported lipid membranes represent a valuable tool to determine physiologically relevant lipid-water partitioning data of pharmaceuticals in an automated setup and is well suited for high-throughput data generation in lead optimization programs.
ISSN:0724-8741
1573-904X
DOI:10.1023/A:1013343117979