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

gold nanoparticle microneedle peptide immunotherapy proinsulin type 1 diabetes

Journal

Immunotherapy advances
ISSN: 2732-4303
Titre abrégé: Immunother Adv
Pays: England
ID NLM: 101776979

Informations de publication

Date de publication:
2022
Historique:
received: 13 09 2021
accepted: 24 01 2022
entrez: 3 8 2022
pubmed: 4 8 2022
medline: 4 8 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 35919496
doi: 10.1093/immadv/ltac002
pii: ltac002
pmc: PMC9327128
doi:

Types de publication

Journal Article

Langues

eng

Pagination

ltac002

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology.

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Auteurs

D Tatovic (D)

Diabetes Research Group, Cardiff University School of Medicine, Cardiff, UK.

M A McAteer (MA)

Midatech Pharma PLC, Cardiff, UK.

J Barry (J)

Midatech Pharma PLC, Cardiff, UK.

A Barrientos (A)

Midatech Pharma PLC, Cardiff, UK.

K Rodríguez Terradillos (K)

Midatech Pharma PLC, Cardiff, UK.

I Perera (I)

Midatech Pharma PLC, Cardiff, UK.

E Kochba (E)

NanoPass Technologies Ltd., Nes Ziona, Israel.

Y Levin (Y)

NanoPass Technologies Ltd., Nes Ziona, Israel.

M Dul (M)

School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.

S A Coulman (SA)

School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.

J C Birchall (JC)

School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.

C von Ruhland (C)

Central Biotechnology Services, Cardiff University, Cardiff, UK.

A Howell (A)

Diabetes Research Group, Cardiff University School of Medicine, Cardiff, UK.

R Stenson (R)

Diabetes Research Group, Cardiff University School of Medicine, Cardiff, UK.

M Alhadj Ali (M)

Diabetes Research Group, Cardiff University School of Medicine, Cardiff, UK.

S D Luzio (SD)

Diabetes Research Unit Cymru, Institute for Life Sciences, Swansea University, Swansea, UK.

G Dunseath (G)

Diabetes Research Unit Cymru, Institute for Life Sciences, Swansea University, Swansea, UK.

W Y Cheung (WY)

Diabetes Research Unit Cymru, Institute for Life Sciences, Swansea University, Swansea, UK.

G Holland (G)

Swansea Trials Unit, Swansea University Medical School, Swansea, UK.

K May (K)

Department of Cellular Pathology, University Hospital of Wales, Cardiff, UK.

J R Ingram (JR)

Division of Infection & Immunity, Cardiff University School of Medicine, Cardiff, UK.

M M U Chowdhury (MMU)

Welsh Institute of Dermatology, University Hospital of Wales, Cardiff, UK.

F S Wong (FS)

Diabetes Research Group, Cardiff University School of Medicine, Cardiff, UK.

R Casas (R)

Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.

C Dayan (C)

Diabetes Research Group, Cardiff University School of Medicine, Cardiff, UK.

J Ludvigsson (J)

Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences and Crown Princess Victoria Children´s Hospital, Linköping University, Linköping, Sweden.

Classifications MeSH