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From the Gut to the Brain: Modeling Intestinal Absorption and Assessing Blood–Brain-Barrier Permeability of Small-Molecule Drugs by IAM Chromatography

Year: 2026

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Designing small-molecule compounds and delivery systems capable of crossing the blood–brain barrier (BBB) remains a major obstacle in central nervous system (CNS) drug development. This challenge is compounded by the lack of robust, rapid, and cost-effective methods for early-stage assessment of BBB permeability. In this study, we addressed this gap by evaluating immobilized artificial membrane (IAM) chromatography as a high-throughput screening tool using a set of 50 marketed drugs with diverse chemical structures and well-documented CNS penetration profiles (both positive and negative). The strong correlation between IAM retention parameters ( k IAM ) and passive diffusion-based permeability confirms the ability of this biomimetic method to simulate drug–membrane interactions, establishing IAM chromatography as a reliable and economical alternative to more complex cell-based and in vivo models. Additionally, the integration of IAM data with in silico molecular descriptors yields a predictive model for intestinal absorption, offering a powerful tool for early permeability profiling in drug discovery.

Source: ACS Omega

DOI: 10.1021/acsomega.6c00701

Authors: Stefan Simić, Predrag Kalaba, Judith Wackerlig, Thierry Langer

Institution: University of Vienna

Language: English

Topic: Barrier Structure and Function Studies

Subfield: Neurology

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,935