Bioinspired virus-like particles which cross the intestinal epithelia to deliver therapeutic cargo

Oral delivery is the easiest way for patients to take drugs. Other routes, like intravenous injections, can be useful because they ensure that 100% of the drug is absorbed into the body. However, injections are painful and can require visits to the clinic and trained healthcare personnel to administer them. This decreases quality of life and decreases the likelihood that patients will stay committed to their treatment. Oral dosage forms, such as pills and drinkable liquids, are much easier and more comfortable for patients to take by themselves. Taking drugs orally is limited though since, for multiple reasons, the body does not easily absorb drugs through the stomach and intestines. This makes it difficult to design drugs which can be taken orally since it would require ingesting large amounts of drug, which can be toxic and expensive. One particularly difficult barrier to absorption is that drugs do not easily pass through the walls of the intestines. Cells of the intestinal wall have evolved to specifically uptake nutrients but exclude foreign substances. Some pathogens - such as cholera, HIV, and norovirus - can either disrupt the intestinal walls or travel through cells and escape the intestines. Particles that could mimic this ability and be loaded with drugs could enable orally administered drugs to be absorbed at levels high enough to sustainably treat disease. The proposed research will design particles, inspired by norovirus, which can pass through the cells of the intestinal wall and deliver their cargo. We will test these particles in human epithelial cells that we culture outside the body, and determine what kind of particles increase absorption the most. If successful, these particles could potentially be loaded with many kinds of drugs and enable their formulation into oral dosage forms which are easier for patients to take, which will increase their health and happiness.