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Titolo:
Solid-supported lipid membranes as a tool for determination of membrane affinity: High-throughput screening of a physicochemical parameter
Autore:
Loidl-Stahlhofen, A; Eckert, A; Hartmann, T; Schottner, M;
Indirizzi:
Nimbus Biotechnol GmbH, D-04229 Leipzig, Germany Nimbus Biotechnol GmbH Leipzig Germany D-04229 D-04229 Leipzig, Germany
Titolo Testata:
JOURNAL OF PHARMACEUTICAL SCIENCES
fascicolo: 5, volume: 90, anno: 2001,
pagine: 599 - 606
SICI:
0022-3549(200105)90:5<599:SLMAAT>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
WATER PARTITION-COEFFICIENTS; ARTIFICIAL MEMBRANES; LIPOSOME-WATER; IN-VITRO; DRUGS; VESICLES; ACIDS; BASES; PHOSPHOLIPIDS; PERMEABILITY;
Keywords:
lipid-water partitioning; lipophilicity; membrane affinity; solid-supported lipid membranes; high-throughput; drug design;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Loidl-Stahlhofen, A Nimbus Biotechnol GmbH, Karl Heine Str 99, D-04229 Leipzig, Germany Nimbus Biotechnol GmbH Karl Heine Str 99 Leipzig Germany D-04229
Citazione:
A. Loidl-Stahlhofen et al., "Solid-supported lipid membranes as a tool for determination of membrane affinity: High-throughput screening of a physicochemical parameter", J PHARM SCI, 90(5), 2001, pp. 599-606

Abstract

Quantification of membrane affinity is an important early screening step in modern drug design. However, current approaches using different lipid membrane models usually are time-consuming or show severe experimental drawbacks. In this paper we describe the use of solid-supported lipid membranes (TRANSIL((R))) as a new tool for the determination of membrane affinity. Eighteen pharmaceuticals (neutrals, acids, and bases) have been analyzed for their lipophilicity at physiological pH in an automated setup; phase separation of lipid and aqueous phase can be achieved simply by a short low-speed centrifugation or filtration. The membrane affinity is then calculated by quantification of the total drug concentration and the amount of drug remaining in the aqueous phase after incubation with solid-supported lipid membranes. Lipophilicity parameters relying on solid-supported lipid membranes correlate well with octanol-water partition coefficients K-ow for neutral organic compounds (range of log K-ow = 1.5-5, n = 7, r = 0.93). Data acquisition with this lipid membrane model system is highly reproducible. Even in thecase of ionizable drugs, where K-ow tends to underestimate membrane affinity, the latter can be correctly quantified using solid-supported lipid membranes: data comparison shows good agreement of the presented approach with established hut time-consuming standardized lipid/buffer systems. Solid-supported lipid membranes allow a fast and reliable quantification of membraneaffinity, enabling high-throughput screening of this physicochemical parameter. (C) 2001 Wiley Liss, Inc. and the American Pharmaceutical AssociationJ Pharm Sci 90:599-606, 2001.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 20:21:02