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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
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 |
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Oxford University Press (OUP)
2022
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URI: | https://cronfa.swan.ac.uk/Record/cronfa61405 |
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2022-10-28T17:04:25.8435381 v2 61405 2022-10-03 Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes 01491e1cd582746a654fad9addf0de16 0000-0002-7206-6530 Steve Luzio Steve Luzio true false fccbba9edcaee08a839a3c5cff8cbe19 0000-0001-6022-862X Gareth Dunseath Gareth Dunseath true false b9f3a8bf7478db012c8856b7bbbc7597 0000-0002-6924-2521 Gail Holland Gail Holland true false a9142ffd398f89eff40ada503e315639 Ivy Cheung Ivy Cheung true false 2022-10-03 MEDS 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. Journal Article Immunotherapy Advances 2 1 Oxford University Press (OUP) 2732-4303 gold nanoparticle, peptide immunotherapy, microneedle, type 1 diabetes, proinsulin 18 3 2022 2022-03-18 10.1093/immadv/ltac002 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee 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). 2022-10-28T17:04:25.8435381 2022-10-03T14:34:04.0797356 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine D Tatovic 0000-0002-3879-2686 1 M A McAteer 2 J Barry 3 A Barrientos 4 K Rodríguez Terradillos 5 I Perera 6 E Kochba 7 Y Levin 8 M Dul 9 S A Coulman 10 J C Birchall 11 C von Ruhland 12 A Howell 13 R Stenson 14 M Alhadj Ali 15 Steve Luzio 0000-0002-7206-6530 16 Gareth Dunseath 0000-0001-6022-862X 17 W Y Cheung 18 Gail Holland 0000-0002-6924-2521 19 K May 20 J R Ingram 21 M M U Chowdhury 22 F S Wong 23 R Casas 24 C Dayan 25 J Ludvigsson 26 Ivy Cheung 27 61405__25610__cdde90b78bb1451dbbd52f8428b7bb00.pdf 61405_VoR.pdf 2022-10-28T17:03:29.4923621 Output 14278267 application/pdf Version of Record true © The Author(s) 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License true eng https://creativecommons.org/licenses/by-nc/4.0/ |
title |
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes |
spellingShingle |
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes Steve Luzio Gareth Dunseath Gail Holland Ivy Cheung |
title_short |
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes |
title_full |
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes |
title_fullStr |
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes |
title_full_unstemmed |
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes |
title_sort |
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes |
author_id_str_mv |
01491e1cd582746a654fad9addf0de16 fccbba9edcaee08a839a3c5cff8cbe19 b9f3a8bf7478db012c8856b7bbbc7597 a9142ffd398f89eff40ada503e315639 |
author_id_fullname_str_mv |
01491e1cd582746a654fad9addf0de16_***_Steve Luzio fccbba9edcaee08a839a3c5cff8cbe19_***_Gareth Dunseath b9f3a8bf7478db012c8856b7bbbc7597_***_Gail Holland a9142ffd398f89eff40ada503e315639_***_Ivy Cheung |
author |
Steve Luzio Gareth Dunseath Gail Holland Ivy Cheung |
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D Tatovic 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 |
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Immunotherapy Advances |
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10.1093/immadv/ltac002 |
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Oxford University Press (OUP) |
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description |
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. |
published_date |
2022-03-18T20:28:35Z |
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1822072887598645248 |
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11.048302 |