Funded by the National Institute of Diabetes and Digestive and Kidney Diseases in collaboration with UF Diabetes Center of Excellence (http://diabetes.ufl.edu/) investigator Michael Clare-Salzler, MD, this 5-year, $1.55M grant (1R01DK091658-01A1) will fund the investigation of biodegradable microparticle formulations delivering immuno-modulatory factors to targeted immune cell types for the prevention and reversal of autoimmune (type 1) diabetes.
Type 1 diabetes is an autoimmune disease with significant personal and economic impact in the US. Therapeutic vaccination approaches for type 1 diabetes hold promise to correct these autoimmune responses. The objective of this proposal is to engineer polymeric biomaterials-based microparticles as an injectable vaccine system to retrain the immune system, correcting aberrant activation toward self-antigens. Specifically, this project focuses on the targeted, controlled delivery of factors (vitamin D, TGF-β1, GM-CSF) and insulin antigen to both intracellular and cell surface receptors of dendritic cells in vivo in order to promote tolerance to diabetes relevant self-antigen. Systemic administration of immune-modulating agents can often result in harmful off-target effects due to uncontrolled dosing of bystander tissues. Encapsulation into biodegradable microparticles can provide targeted, controlled delivery of these agents, reducing the total dose required and limiting off-target effects.