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Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes
,
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 ,
Gareth Dunseath ,
W Y Cheung,
Gail Holland ,
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 , Gareth Dunseath , Gail Holland , Ivy Cheung
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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...
| Published in: | Immunotherapy Advances |
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| ISSN: | 2732-4303 |
| Published: |
Oxford University Press (OUP)
2022
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa61405 |
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| 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. |
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| 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 |