Details zur Publikation |
| Kategorie | Textpublikation |
| Referenztyp | Zeitschriften |
| DOI | 10.1016/j.ejps.2025.107354 |
Lizenz  |
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| Titel (primär) | Blood-brain barrier permeability revisited: predicting intrinsic passive BBB permeability using the solubility-diffusion model |
| Autor | Ebert, A.
; Goss, K.-U. |
| Quelle | European Journal of Pharmaceutical Sciences |
| Erscheinungsjahr | 2025 |
| Department | COMPBC |
| Band/Volume | 215 |
| Seite von | art. 107354 |
| Sprache | englisch |
| Topic | T9 Healthy Planet |
| Supplements | Supplement 1 Supplement 2 |
| Keywords | Blood brain barrier; Caco-2; MDCK; intrinsic membrane permeability; solubility-diffusion model; size limit; PAMPA |
| Abstract | Passive permeability is a critical parameter for modeling drug uptake across the blood-brain barrier (BBB). In this work, we tested the hypothesis that intrinsic passive BBB permeability (P0,BBB) is equivalent to intrinsic membrane permeabilities measured in Caco-2 or MDCK assays, and that it can also be predicted using the solubility-diffusion model (SDM). To evaluate this, we re-analyzed brain perfusion data from the literature, excluding measurements limited by processes other than passive membrane permeation, such as flow limitation, paracellular transport, or active transport. The resulting membrane-limited P0 dataset (N = 84), spanning approximately six orders of magnitude, was well predicted by Caco-2/MDCK permeabilities of experimental origin (RMSE = 0.86; N = 34). SDM predictions based on hexadecane/water partition coefficients estimated by COSMOtherm and various LSER methods showed satisfactory performance (RMSE = 1.73-2.29; N = 84), with notable improvement observed for small molecules (MW < 500 g/mol; RMSE = 1.32-1.93; N = 70). No evidence for a molecular size cutoff was found. The approach was also successfully applied to zwitterionic compounds. The findings demonstrate that P0 values in the BBB are directly comparable to Caco-2/MDCK assays, and that the SDM is a valuable tool for predicting BBB permeability, with the potential to complement or partially replace more resource-intensive in vitro assays. |
| dauerhafte UFZ-Verlinkung | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=31499 |
| Ebert, A., Goss, K.-U. (2025): Blood-brain barrier permeability revisited: predicting intrinsic passive BBB permeability using the solubility-diffusion model Eur. J. Pharm. Sci. 215 , art. 107354 10.1016/j.ejps.2025.107354 |
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