Transdermally delivered tolerogenic nanoparticles induced effective immune tolerance for asthma treatment

Jiaxuan Zhao, Penghui He, Min Jiang, Chunting He, Yuanhao Zhao, Zhihua Zhang, Zhibing Zhang, Guangsheng Du*, Xun Sun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Induction of antigen-specific immune tolerance for the treatment of allergic or autoimmune diseases is an attractive strategy. Herein, we investigated the protective effect of a transdermal microneedle patch against allergic asthma by stimulating allergen-specific immune tolerance. We fabricated biodegradable tolerogenic nanoparticles (tNPs) that are loaded with a model allergen ovalbumin (OVA) and an immunomodulator rapamycin, and filled the tNPs into microneedle tips by centrifugation to form sustained-release microneedles. After intradermal immunization, the microneedles successfully delivered the cargos into the skin and sustainedly released them for over 96 h. Importantly, the microneedles induced allergen-specific regulatory T cells (Treg), decreased the levels of pro-inflammatory cytokines and antibodies while increased anti-inflammation cytokines, finally leading to restored immune homeostasis. The lung tissue analysis illustrated that the sustained-release microneedles significantly reduced the infiltration of eosinophils, decreased the accumulation of mucus and collagen, and significantly relived asthma symptoms. Our results suggested that the sustained-release microneedle-based transdermal delivery system can induce antigen-specific immune tolerance with improved compliance and efficacy, providing a new therapeutic strategy for the treatment of allergic and autoimmune diseases.

Original languageEnglish
Pages (from-to)637-649
Number of pages13
JournalJournal of Controlled Release
Volume366
Early online date17 Jan 2024
DOIs
Publication statusPublished - Feb 2024

Bibliographical note

Acknowledgments:
We acknowledge the support by National Natural Science Foundation of China (No. 82320108020 & 81925036 & 82003684), Natural Science Foundation of Sichuan Province (No. 2022NSFSC1491), China Postdoctoral Science Foundation Grant (2019 M663534, China), Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System (CARS-SVDIP, China), the Fundamental Research Funds for the Central Universities and Sichuan University Postdoctoral Interdisciplinary Innovation Fund.

Copyright:
© 2024 Elsevier B.V. All rights reserved.

Keywords

  • Polymeric microneedles
  • Allergen-specific immune tolerance
  • Allergic asthma
  • Sustained release
  • Hyaluronic acid

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