Targeting toxic gut lymph to treat acute disease
Acute disease (AD) is usually managed in emergency and intensive care settings, and includes sepsis, trauma, haemorrhagic shock and pancreatitis. Worldwide, 20 million people per year are admitted to intensive care units with AD and of these 30% die. Death results when AD progresses from an acute systemic inflammatory response syndrome (SIRS) to multiple organ dysfunction syndrome (MODS). Current management of AD is generic, including fluid resuscitation, enteral feeding, antibiotics and vital organ support. Effective and disease specific treatments that stop the progression to SIRS, MODS and organ failure are critically needed. Recent findings in our collaborators lab have identified gut-lymph as a source of toxic factors that promote SIRS and MODS. According to the gut-lymph hypothesis blood flow to abdominal organs is reduced in AD in order to maintain perfusion of vital organs. This results in gut ischemia and breakdown, and the release of toxic factors that drain into the gut-lymph. Toxic gut-lymph flows into the thoracic lymph, bypasses the liver and enters the systemic circulation via the subclavian vein. Toxic gut-lymph subsequently damages vital organs remote from the gut. This project will address the gap in effective and disease-specific treatments for AD via the development of approaches to target candidate treatments to gut-lymph. The project aims to: 1. Develop novel drug delivery systems to target gut-lymph in AD, 2. Demonstrate that gut-lymph targeted delivery systems facilitate improved treatment of experimental AD. The project will involve interaction with our synthetic chemistry team and AD specialists in NZ. The student will receive training in drug delivery and pharmacokinetics, cell culture, analysis (LC-MS-MS) and AD models.