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Endocrine Abstracts (2022) 86 P70 | DOI: 10.1530/endoabs.86.P70

1Centre for Cardiovascular Science, QMRI, Edinburgh, United Kingdom; 2University of Nottingham Biodiscovery Institute, Nottingham, United Kingdom; 3MRC Centre for Regenerative Medicine, Edinburgh, United Kingdom

Background: Islet transplant into the liver is a therapy for type 1 diabetes patients experiencing severe hypoglycaemia or impaired hypoglycaemic awareness. Widespread use is not currently considered due to the requirement for immunosuppression for the lifetime of the graft, and the attrition in graft function over the following 1-5 years. Following transplant into the liver, inflammation results in >60% islet loss, with few patients achieving insulin independence. The liver contains a high density of asialoglycoprotein receptors (ASGPR) with high affinity for galactose. Poly(lactic-co-glycolic acid) (PLGA) is an FDA approved, biodegradable polymer which can be manufactured into microparticles. We hypothesised that particles expressing galactose may target the liver and in the future may be loaded with anti-inflammatory and/or pro-vascularisation agents to help reduce islet inflammation and improve islet vasculature.

Aim: To test if galactosylated PLGA ((PLGA-Gal)) microparticles target the liver and to determine the optimal microparticle size and dose.

Methods: Fluorescent PLGA-Gal microparticles were injected into the liver in mice. A range of diameters (13 um and 20 um), doses (0.1 mg and 1 mg) and controls (PLGA-Gal and non-galactosylated microparticles) were tested. Biodistribution was assessed to find optimum microparticle size and dose that specifically located to the liver without necrosis.

Results: 13 um PLGA-Gal microparticles located specifically to the liver with least necrotic effects when at 0.1 mg dose. 20 um microparticles and 1 mg dose of all microparticles were associated with liver necrosis at day 1 and 3 post-transplant, which resolved by day 7 post-transplant.

Conclusion: PLGA-Gal microparticles target the liver specifically; 0.1 mg of 13 um microparticles are associated with minor liver necrosis (compared to the more severe necrosis seen with all other formulations and doses) and may be developed to encapsulate factors that promote islet engraftment and vascularisation to improve islet survival.

Volume 86

Society for Endocrinology BES 2022

Harrogate, United Kingdom
14 Nov 2022 - 16 Nov 2022

Society for Endocrinology 

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