Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes. Issue 1 (27th January 2022)

• Record Type: Journal Article
• Authors: Tatovic, D; McAteer, M A; Barry, J; Barrientos, A; Rodríguez Terradillos, K; Perera, I; Kochba, E; Levin, Y; Dul, M; Coulman, S A; Birchall, J C; von Ruhland, C; Howell, A; Stenson, R; Alhadj Ali, M; Luzio, S D; Dunseath, G; Cheung, W Y; Holland, G; May, K; Ingram, J R; Chowdhury, M M U; Wong, F S; Casas, R; Dayan, C; Ludvigsson, J
• Is Part Of: Immunotherapy advances. Volume 2:Issue 1(2022)
• Publication Date: 2022-01-27
• Subjects: gold nanoparticle -- peptide immunotherapy -- microneedle -- type 1 diabetes -- proinsulin; Immunotherapy -- Periodicals; 615.37
• DOI: 10.1093/immadv/ltac002
• Languages: English
• ISSNs: 2732-4303

Abstract

Abstract: Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune β-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 (GNPs), 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 Graphical Abstract: