TY - JOUR
T1 - Microneedles coated with peanut allergen enable desensitization of peanut sensitized mice
AU - Shakya, Akhilesh Kumar
AU - Ingrole, Rohan S.J.
AU - Joshi, Gaurav
AU - Uddin, Md Jasim
AU - Anvari, Sara
AU - Davis, Carla M.
AU - Gill, Harvinder Singh
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/11/28
Y1 - 2019/11/28
N2 - The prevalence of peanut allergies has escalated over the last 20 years, yet there are no FDA approved treatments for peanut allergies. In this study we evaluated the potential of microneedles to deliver peanut protein extract (PE) into skin and assessed if the ensuing immune responses could desensitize mice that were sensitized to peanuts. Peanut sensitized mice were either treated through cutaneous immunotherapy using PE-coated microneedles or not treated, and then orally challenged with PE. After oral challenge, the clinical symptoms of peanut-induced anaphylaxis were significantly lower in the microneedle treated mice as compared to untreated mice, and this was accompanied by down-regulation of systemic anaphylaxis mediators such as histamine and mast cell protease-1 (MCPT-1) in the microneedles treated group. Overall, there was an up-regulation of Th1 cytokines (IL-2 and IFN-γ) as compared to Th2 cytokines (IL-4 and IL-5) in splenocyte culture supernatants of the microneedle treated group as compared to untreated group, suggesting that microneedles promoted immune modulation towards the Th1 pathway. Furthermore, mice treated with PE-coated microneedles were observed to retain integrity of their small intestine villi and had reduced eosinophilic infiltration as compared to the untreated but peanut sensitized mice, which further confirmed the desensitization capability of peanut cutaneous immunotherapy using coated microneedles. Thus, our current study represents a novel minimally invasive microneedle based cutaneous immunotherapy, which may provide a novel route of desensitization for the treatment of peanut allergies.
AB - The prevalence of peanut allergies has escalated over the last 20 years, yet there are no FDA approved treatments for peanut allergies. In this study we evaluated the potential of microneedles to deliver peanut protein extract (PE) into skin and assessed if the ensuing immune responses could desensitize mice that were sensitized to peanuts. Peanut sensitized mice were either treated through cutaneous immunotherapy using PE-coated microneedles or not treated, and then orally challenged with PE. After oral challenge, the clinical symptoms of peanut-induced anaphylaxis were significantly lower in the microneedle treated mice as compared to untreated mice, and this was accompanied by down-regulation of systemic anaphylaxis mediators such as histamine and mast cell protease-1 (MCPT-1) in the microneedles treated group. Overall, there was an up-regulation of Th1 cytokines (IL-2 and IFN-γ) as compared to Th2 cytokines (IL-4 and IL-5) in splenocyte culture supernatants of the microneedle treated group as compared to untreated group, suggesting that microneedles promoted immune modulation towards the Th1 pathway. Furthermore, mice treated with PE-coated microneedles were observed to retain integrity of their small intestine villi and had reduced eosinophilic infiltration as compared to the untreated but peanut sensitized mice, which further confirmed the desensitization capability of peanut cutaneous immunotherapy using coated microneedles. Thus, our current study represents a novel minimally invasive microneedle based cutaneous immunotherapy, which may provide a novel route of desensitization for the treatment of peanut allergies.
KW - Allergen
KW - Allergen immunotherapy
KW - Coated microneedles
KW - Cutaneous immunotherapy
KW - Food allergy
KW - Microneedles
KW - Peanut allergy
KW - Skin vaccination
UR - http://www.scopus.com/inward/record.url?scp=85074018301&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2019.09.022
DO - 10.1016/j.jconrel.2019.09.022
M3 - Article
C2 - 31626861
AN - SCOPUS:85074018301
VL - 314
SP - 38
EP - 47
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -