Safety of the use of Gold Nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in Type 1 diabetes
Tatovic D., McAteer MA., Barry J., Barrientos A., Rodríguez Terradillos K., Perera I., Kochba E., Levin Y., Dul M., Coulman SA., Birchall JC., von Ruhland C., Howell A., Stenson R., Alhadj Ali M., Luzio SD., Dunseath G., Cheung WY., Holland G., May K., Ingram JR., Chowdhury MMU., Wong FS., Casas R., Dayan C., Ludvigsson J.
Abstract Antigen-specific immunotherapy is immunomodulatory strategy for autoimmune diseases, such as Type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune beta-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNP), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well-tolerated in participants with Type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.