Delivery of allergen powder for safe and effective epicutaneous immunotherapy.
J Allergy Clin Immunol
; 145(2): 597-609, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31783055
ABSTRACT
BACKGROUND:
More effective and safer immunotherapies to manage peanut allergy are in great demand despite extensive investigation of sublingual/oral immunotherapy and epicutaneous immunotherapy (EPIT) currently in the clinics.OBJECTIVE:
We sought to develop a powder-laden, dissolvable microneedle array (PLD-MNA) for epidermal delivery of powdered allergens and to evaluate the efficacy of this novel EPIT in peanut-sensitized mice.METHODS:
PLD-MNA was packaged with a mixture of powdered peanut allergen (PNA), 1,25-dihydroxyvitamin D3 (VD3), and CpG. Its epidermal delivery and therapeutic efficacy were evaluated alongside PNA-specific forkhead box P3-positive regulatory T cells and IL-10+ and TGF-ß1+ skin-resident macrophages.RESULTS:
PLD-MNA was successfully laden with PNA/VD3/CpG powder and capable of epidermal delivery of most of its content 1 hour after application onto intact mouse skin concomitant with no significant leakage into the circulation or skin irritation. PLD-MNA-mediated EPIT substantially reduced clinical allergy scores to 1 from 3.5 in sham control mice (P < .001) after 6 treatments accompanied by lower levels of PNA-specific IgE and intestinal mucosal mast cells and eosinophils over sham treatments. Moreover, in comparison with allergens administered intradermally, powdered allergens delivered by means of PLD-MNA preferentially attracted immunoregulatory macrophages and stimulated the cells to produce IL-10, TGF-ß, or both at the immunization site, which might account for increased numbers of regulatory T-like cells in lymph tissues in association with systemic tolerance. PNA/VD3/CpG-laden PLD-MNA was safe and required only 6 treatments and one fifth of the PNA adjuvant dose, with improved outcomes when compared with 12 conventional intradermal immunotherapies.CONCLUSIONS:
PLD-MNA holds great promise as a novel, safe, effective, and self-applicable modality to manage IgE-mediated allergies.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Alérgenos
/
Dessensibilização Imunológica
/
Sistemas de Liberação de Medicamentos
/
Hipersensibilidade a Amendoim
Limite:
Animals
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2020
Tipo de documento:
Article