作者
Shakhawath Hossain, Paul Joyce, Albin Parrow, Silver Jõemetsa, Fredrik Höök, Per Larsson, Christel AS Bergström
发表日期
2020/9/22
期刊
Molecular pharmaceutics
卷号
17
期号
11
页码范围
4226-4240
出版商
American Chemical Society
简介
Transient permeability enhancers (PEs), such as caprylate, caprate, and salcaprozate sodium (SNAC), improve the bioavailability of poorly permeable macromolecular drugs. However, the effects are variable across individuals and classes of macromolecular drugs and biologics. Here, we examined the influence of bile compositions on the ability of membrane incorporation of three transient PEs—caprylate, caprate, and SNAC—using coarse-grained molecular dynamics (CG-MD). The availability of free PE monomers, which are important near the absorption site, to become incorporated into the membrane was higher in fasted-state fluids than that in fed-state fluids. The simulations also showed that transmembrane perturbation, i.e., insertion of PEs into the membrane, is a key mechanism by which caprylate and caprate increase permeability. In contrast, SNAC was mainly adsorbed onto the membrane surface …
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S Hossain, P Joyce, A Parrow, S Jõemetsa, F Höök… - Molecular pharmaceutics, 2020