Associated organisationsUniversity of Edinburgh · University of NottinghamEurope PMC affiliations are not treated as award recipients or mapped locations.
Funding£3.0M
PeriodMar 2024 — Sept 2028
In plain English
AI plain-English summary
Most transplanted islets—the insulin-producing cells that could cure Type 1 diabetes—are destroyed within days by inflammation and immune attack, even when the procedure works. Researchers have developed biodegradable microparticles, smaller than a grain of salt, that carry anti-inflammatory and pro-regenerative drugs directly to the liver, where islets are implanted. In diabetic mice, a single dose of these drug-loaded particles—at a fraction of the systemic dose—significantly improved blood sugar control. This matters because islet transplantation currently rarely achieves long-term insulin independence. The immune system and inflammation kill most transplanted cells, forcing patients to remain on insulin. The particles are made from a polymer already approved for use in human pharmaceuticals, and they target the liver specifically via a sugar molecule that binds to a receptor found only on liver cells. If this approach works in human trials, it could transform islet transplantation from a temporary stabilisation procedure into a reliable, long-term treatment that frees people with Type 1 diabetes from daily insulin injections. The team will test the particles in large animal models and on human liver tissue, then work with a regulatory body to prepare for clinical use.
View original technical description
Islet transplantation into the liver of someone with Type 1 diabetes stabilises blood glucose control but rarely results in insulin independence, as most islets are destroyed post-transplant from inflammation and immune-mediated mechanisms. We have developed microparticles (MPs) from the polymer poly(DL-lactic-co-glycolic acid): a biodegradable material used in pharmaceutical formulations in which drugs can be loaded and their release controlled. The polymer has a galactose (Gal) moiety attached to it and targets the liver via the liver-specific asialoglycoprotein receptor (ASGPR). We have determined the safe and effective dose of specific anti-inflammatory and pro-regenerative drugs which significantly improves glycaemic control in a diabetic mouse model transplanted with islets via the portal vein. Importantly, the effective dose of drugs is a fraction of the systemic dose required. Our objectives are to : 1. Develop a range of Gal-MPs packaged individually with anti-inflammatory/immunomodulatory and pro-regenerative drugs (Drug-Gal-MPs) to target the liver with appropriate release kinetics; 2. Demonstrate efficacy/safety/mechanism of action of islets co-transplanted with these Drug-Gal-MPs including Drug-MPs in combination; 3. Understand regulatory landscape. We will assess the: 1. Release kinetics of other Drug-Gal-MPs already developed; 2. Biodistribution /pharmacokinetics of Drug-Gal-MPs; 3. Short-term effects of Gal-MPs on liver; 4. Long-term metabolic effects of Gal-MPs. We will develop the most efficacious Drug-Gal-MPs to GLP-grade, test in small and large animal models with islets including ex-vivo in human liver. We will explore the Drug-Gal-MPs with hESC islets through our collaborators and work with Catapult to understand the regulatory landscape to develop the Drug-Gal-MPs for clinical use.
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