Novel oral oleosomes formulations of immunomodulatory agents to improve treatment outcomes of inflammatory bowel disease

About the Project

Inflammatory bowel disease (IBD) is an autoimmune condition in which the immune system attacks its own intestinal tissue. It could be divided into two major subtypes: Ulcerative colitis and Crohn’s disease. Targeted delivery of immunomodulatory agents to the lymph nodes that drain the majority of the gastrointestinal tract (mesenteric lymph nodes) and play an important role in the pathophysiology of IBD has potential to improve substantially the treatment of outcomes of this devastating condition. Lipid-based formulations composed of long chain triglycerides facilitate the intestinal lymph nodes targeting and higher systemic bioavailability through chylomicrons (CMs) pathway.

Cannabidiol (CBD) is a highly lipophilic non-psychoactive phytocannabinoid derived from Cannabis plant with immunomodulatory properties. It activates endocannabinoid system and regulates inflammatory cytokines, such as IL-6 and TNF-α. However, due to the high lipophilicity and substantial first pass metabolism, CBD has limited oral bioavailability of around 8%. Co-administration of CBD with long chain triglyceride facilitates the oral bioavailability and intestinal lymphatic targeting of this compound. However, the bioavailability of CBD is still limited to around 20-25% using conventional lipid-based drug delivery systems.

Oleosomes are natural lipid droplets found in various seeds. They are an important as an energy source necessary for germination. The structure of oleosomes is similar to lipoproteins (0.5- 2.5 μm in diameter) with the surface coated by vegetable proteins, while the core contains large amounts of oils at low oxidative state.

We have recently found that oleosomes-based oral lipid drug delivery systems of CBD lead to highest oral bioavailability of the drug (around 50%) reported so far in the literature. The concentrations of the drug in mesenteric lymph nodes are also extremely high with prominent reduction in TNF-α level. Using these exciting preliminary data, we have recently obtained a substantial external funding to assess the efficacy of these promising formulations of CBD in various animal models of IBD.

Therefore, the aims of this PhD project will be focused on establishment of animal models of IBD, and demonstration of the efficacy of oleosomes-based formulations of CBD in these animal models. We have active collaboration with IBD scientists and clinicians based in the USA, and the PhD student will have an opportunity to conduct some of the experiments both in the UK and in the USA.

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, Preclinical Models and Clinical Medicine.

The project will be supervised by Dr Pavel Gershkovich in the University of Nottingham, UK: https://www.nottingham.ac.uk/pharmacy/people/pavel.gershkovich

Funding Notes

Applications are invited from self-funded students. Substantial external funding has been secured for the experimental work and associated travel expenses between collaborating laboratories in the UK and USA.