Organ-on-a-Chip Network & Emulate Proof of Concept Award
Towards a biomicrofluidic model of the enterocyte-lymphatic interface to study the intestinal transport of lipid-soluble drugs
SummaryThe cost of bringing a drug candidate to market is approximately US$ 1 billion. This can be partially attributed to the testing of drugs on models that fail to predict how they will behave in humans. For example, orally administered drugs fail pre-clinical evaluation more often than not as models of the gut do not accurately predict how bioavailable a drug will be in humans.
Animal models are frequently used in drug testing and are useful to understand how a drug behaves in a living organism, however, they are inherently limited in that they have different gut physiology to our own. Human cells grown in petri dishes are also used in drug testing, although they do not experience the dynamic forces that cells in our own bodies experience. With this in mind, we aim to develop a model where human gut cells are grown in small microchannels and perfused with biological fluids to capture the physiology of the human gut.
The lymphatic system is a vascular network responsible for trafficking immune cells, draining fluid from the tissues, and delivering dietary fats to the circulation. Fats are packaged into small vesicles, termed lipoproteins, by the gut before they are delivered to the blood via the lymphatics. The movement of fats by the lymphatics is critical to the maintenance of human health, however, we do not fully understand the mechanisms behind this process due to the absence of an appropriate lymphatics model. Additionally, we now know that some drugs can be carried to the blood by lipoproteins via the lymphatics which increases their bioavailability by avoiding initial metabolism by the liver. By incorporating human lymphatic cells into our model, it can be utilised to study how dietary fats are transported and could be used to screen therapeutics that target the lymphatic system.