Endocrine Abstracts (2012) 28 AP1.3

Nanomedicine in clinical diabetes

John Pickup

King's College London School of Medicine, Guy's Hospital, London, United Kingdom.

Opportunities for applications of nanomedicine in diabetes are numerous. In type 1 diabetes, improved insulin replacement is urgently needed, but transplantation of islet cells is not routine, limited by availability of human islets and immune rejection. Longer survival of transplanted islets might be ensured by nano-encapsulation technologies which protect the islets from early cell death caused by the inflammatory in vivo environment and isolate against later immune rejection. We have found that allogeneic transplantation of mouse islets encapsulated with nanofilms made by layer-by-layer application of biocompatible polysaccharides have improved survival compared to naked islets when transplanted into diabetic animals. The technology might also be useful in the future for transplanted xenographs and stem cells. In type 2 diabetes, early introduction of insulin is often resisted, but switching to insulin might be encouraged by non-injectable insulins such as nano-formulations of inhaled or oral insulin, where layer-by-layer nano-encapsulation of the protein may be a suitable formulation. In both types of diabetes, more stable and accurate continuous glucose monitoring is needed. We are researching nanosecond fluorescence lifetime photonics as a glucose detection technology. Unlike present electrochemical glucose sensors, fluorescence lifetime-based sensors are not subject to interference from electroactive substances in the tissues. Mutants of glucose/galactose-binding protein (GBP) with a high binding constant have been engineered and labelled with the fluorophore, badan. Glucose binding causes conformational change in the GBP and increased fluorescence lifetime and intensity. Prototype fibre optic glucose sensors for subcutaneous implantation, based on GBP, have been constructed and tested. GBP-badan microvesicles have been fabricated and might be implanted eventually in skin as a ‘smart tattoo’-type of non-invasive glucose sensor. Since closing-the-loop by coupling glucose monitoring to insulin delivery using electromechanical devices is complex and has not reached routine practice, the possibilities of developing an ‘artificial nanopancreas’ should be considered.

Declaration of interest: There is no Declaration of interest of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: Declaration of Funding: This work was supported by the EPSRC, the Diabetes Foundation and the European Foundation for the Study of Diabetes.

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