No Cover Image

Journal article 65 views 8 downloads

Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes

D Tatovic Orcid Logo, M A McAteer, J Barry, A Barrientos, K Rodríguez Terradillos, I Perera, E Kochba, Y Levin, M Dul, S A Coulman, J C Birchall, C von Ruhland, A Howell, R Stenson, M Alhadj Ali, Steve Luzio Orcid Logo, Gareth Dunseath Orcid Logo, W Y Cheung, Gail Holland Orcid Logo, K May, J R Ingram, M M U Chowdhury, F S Wong, R Casas, C Dayan, J Ludvigsson, Ivy Cheung

Immunotherapy Advances, Volume: 2, Issue: 1

Swansea University Authors: Steve Luzio Orcid Logo, Gareth Dunseath Orcid Logo, Gail Holland Orcid Logo, Ivy Cheung

  • 61405_VoR.pdf

    PDF | Version of Record

    © The Author(s) 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License

    Download (13.62MB)

Check full text

DOI (Published version): 10.1093/immadv/ltac002

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...

Full description

Published in: Immunotherapy Advances
ISSN: 2732-4303
Published: Oxford University Press (OUP) 2022
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa61405
Tags: Add Tag
No Tags, Be the first to tag this record!
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.
Keywords: gold nanoparticle, peptide immunotherapy, microneedle, type 1 diabetes, proinsulin
College: Faculty of Medicine, Health and Life Sciences
Funders: This work has been funded through the EE-ASI (The Enhanced Epidermal Antigen Specific Immunotherapy Against Type 1 Diabetes) European research network (Collaborative Project) supported by the European Commission under the Health Cooperation Work Programme of the 7th Framework Programme (grant no. N 305305).
Issue: 1