Achieving oral delivery of biotherapeutics is crucial for development of treatments accessible to everyone. Design of oral therapies requires understanding of how they cross the gastrointestinal tissue barrier. Multiple individual components of gastrointestinal mucosa (mucus, degradative enzymes, epithelium) contribute to the overall barrier, but the subepithelial basement membrane (BM) remains the least characterised barrier. Here we will characterize how biotherapeutics navigate the dense mesh of epithelial BM barrier. We will use state-of-the-art computer modelling and cell culture tools to quantify the diffusion of macromolecules across the intestinal epithelial BM, with a goal to inform on rational drug delivery and toxicology.
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