Targeting drugs to the intestinal lymphatic system for improved treatment of autoimmune conditions, cancer and HIV

About the Project

Intestinal system plays an important role in the pathophysiology of a number of diseases, including autoimmune conditions, cancer and HIV. Therefore, efficient delivery of drugs to the intestinal lymphatic system has potential to improve treatment of these conditions. However, only a very limited proportion of the administered dose can usually be distributed from the systemic circulation into the lymphatic system. Therefore, there is an unmet need for efficient delivery of therapeutic agents to the intestinal lymphatics for treatment of patients affected by diseases associated with the intestinal lymphatic system.

Although most drugs absorbed from the gastrointestinal (GI) system are passed to the portal vein, lipophilic compounds may also gain access to systemic circulation through the intestinal lymphatics. This distribution to the lymphatic system is determined mainly by the association of drugs with large lipoproteins, i.e. chylomicrons, in the enterocytes. This is because drug molecules need to bind to chylomicrons in order to utilise them as a carrier to the lymphatic system.

It is known that if a drug has the necessary physicochemical properties, an appropriate lipid-based formulation can facilitate the transport of the drug via the intestinal lymphatic system following oral administration. On the other hand, lipophilic prodrug approaches could be employed to take advantage of the intestinal lymphatic transport of drug molecules that otherwise would not have the necessary physicochemical properties required for association with chylomicrons.

In this project, depending on the physicochemical properties of candidate molecules, we will deliver anticancer, antiretroviral or immunomodulatory compounds to the intestinal lymphatic system using lipid-based drug delivery approach with or without chemical prodrug modifications.

PhD student involved in this project will have a unique opportunity to learn skills and knowledge highly sought after by both pharmaceutical industry and academia, including Biopharmaceutics, Pharmacokinetics, Pharmacodynamics, Drug Delivery, and Preclinical Models.

For informal inquiries please contact Dr Pavel Gershkovich: pavel.gershkovich@nottingham.ac.uk

Funding Notes

Applications are invited from self-funded students.