Details

Autor(en) / Beteiligte

• Sugano, K.

Titel

5.19 - Artificial Membrane Technologies to Assess Transfer and Permeation of Drugs in Drug Discovery

Ist Teil von

• Comprehensive Medicinal Chemistry II, 2007, Vol.5, p.453-487

Auflage

Second Edition

Ort / Verlag

Elsevier Ltd

Erscheinungsjahr

2007

Link zum Volltext

Beschreibungen/Notizen

• The passive transfer and permeation of drugs across a membrane are important determinants of ADME processes, and are related to the physicochemical properties of drugs. Recently, it has become possible to assess the passive membrane permeation-utilizing artificial membrane technologies that mimic real biological membranes. The artificial membrane technologies can be mapped at the intersection of the biological and physicochemical approaches. Biological membranes have a large variation among each organ. The intestinal brush border membrane and the blood–brain barrier membrane are mainly composed of phospholipids. The skin permeation barrier (the intercellular lipids of the stratum corneum) is mainly composed of ceramides, cholesterol, and free fatty acids. These lipids organize a lipophilic permeation barrier for hydrophilic molecules. The permeation process across a lipophilic permeation barrier is theoretically described by the solubility–diffusion model and/or the two-step (flip-flop) model. Artificial membrane tools for drug discovery can be categorized into two types: permeation across the membrane (e.g., the parallel artificial membrane permeation assay and Fluorosome) and partition into the membrane (e.g., immobilized artificial membrane (IAM) column chromatography, immobilized liposome chromatography, liposome electrokinetic chromatography, pH titration, the surface plasmon resonance-based method, and the solid-supported lipid membrane). These technologies are reviewed from the viewpoint of in vivo predictability and drug discovery utility.