Tissue barriers help maintain homeostasis through the regulation of transport to and from the blood circulation. While this process is critical for adequate organ function, it is also a major hurdle for targeted drug delivery. Depending on the route of administration, therapeutic drugs need to cross one or multiple tissue barriers that substantially restrict their permeability. In the case of drug delivery to the brain, transport from the blood circulation into the brain parenchyma can occur through either the endothelial cells at the blood-brain barrier or the epithelial cells at the choroid plexus. While the molecular mechanisms responsible for the transport of small molecular weight chemical compounds are well described, less is known about the transport pathways for biologics (e.g. proteins, nanoparticles, viruses). Characterization of the mechanisms for transport of biologics across tissue barriers is key to improve targeted drug delivery.

The goal of this Methods Collection is to provide examples of assays used to measure the transport of biologics across tissue barriers, including the blood-brain barrier, blood-CSF barrier, blood-retinal barrier, and the intestine. The Collection highlights recent methods in microscopy (total internal reflection microscopy, light-sheet microscopy) and in vitro modeling (organoids, micro-physiological systems) applied to tissue barriers. It is a resource for scientists interested in targeted drug delivery and tissue barrier physiology.