Role of the Basement Membrane as an Intestinal Barrier to Absorption of Macromolecules and Nanoparticles

Full understanding of the barrier property of mucosal tissues is imperative for development of successful mucosal drug delivery strategies, particularly for biologics and nanomedicines. The contribution of the mucosal basement membrane (BM) to this barrier is currently not fully appreciated. This work examined the role of the BM as a barrier to intestinal absorption of model macromolecules (5 and 10 kDa dextrans) and 100 nm polystyrene nanoparticles. Dextrans and nanoparticles were applied either directly to BM-coated inserts or to an intestinal model, namely, differentiated intestinal epithelial monolayers (Caco-2) cultured on BM-modified inserts. The work shows that the BM per se does not impact the diffusion of dextran macromolecules but severely hinders the movement of nanoparticles. However, importantly, Caco-2 monolayers cultured on BM-coated inserts, which show a remarkably different morphology, display a significantly larger barrier to the translocation of one dextran, as well as nanoparticle syst...