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  Oral Insulin delivery using GET peptide technology


   School of Pharmacy

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  Dr J Dixon, Prof K Shakesheff  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: higher patient compliance, rapid hepatic insulinisation, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The main barriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium. Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success.

We have created a method of efficiently delivering drugs into cells by targeting a ubiquitous sugar type (Heparan sulphate expressed on cell membranes with a cell penetrating peptide (CPP) (PNAS, 2016). We term our delivery system as glycosaminoglycan-binding enhanced transduction (GET) which is being patented by the University of Nottingham (PCT/GB2014/053764).

http://www.ukrmp.org.uk/hubs/acellular/our-research-team/university-of-nottingham-dr-james-dixon/

This project will exploit GET peptides and new derivatives with the aim to promote the intracellular transduction of Insulin and subsequent release into the systemic circulation. We have exciting preliminary data showing modification of GET with transcytosis peptides can improve insulin delivery through biological barriers. My group is currently working on many aspects of the core GET technology all with the aim to translate our work towards regenerative medicine applications. Training will be given in all aspects of the project including recombinant protein production, cell culture, immunostaining, microscopy (fluorescence, confocal, SEM), biochemical assays.

Funding Notes

Applications are invited from self-funded students. For informal enquiries please contact Dr James Dixon ([Email Address Removed]).

References

Dixon et al. (2016). Highly Efficient Delivery of Functional Proteins by the Synergistic Effect of GAG Binding Motifs and Cell-Penetrating Peptides. PNAS. 113. 3. E291-299.

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