Tatovic, D.  ORCID: https://orcid.org/0000-0002-3879-2686, McAteer, M. A., Barry, J., Barrientos, A., Rodríguez Terradillos, K., Perera, I., Kochba, E., Levin, Y., Dul, M., Coulman, S. A. ORCID: https://orcid.org/0000-0002-1277-7584, Birchall, J. C. ORCID: https://orcid.org/0000-0001-8521-6924, 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. ORCID: https://orcid.org/0000-0002-5257-1142, Chowdhury, M. M. U., Wong, F. S. ORCID: https://orcid.org/0000-0002-2812-8845, Casas, R., Dayan, C. ORCID: https://orcid.org/0000-0002-6557-3462 and Ludvigsson, J.
2022.
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in Type 1 diabetes.
Immunotherapy Advances
2
(1)
, ltac002.
10.1093/immadv/ltac002
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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.
| Item Type: | Article |
|---|---|
| Date Type: | Published Online |
| Status: | Published |
| Schools: | Medicine Pharmacy |
| Additional Information: | This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| ISSN: | 2732-4303 |
| Date of First Compliant Deposit: | 15 February 2022 |
| Date of Acceptance: | 9 December 2021 |
| Last Modified: | 07 May 2023 18:46 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/147484 |
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