Sustained antigens delivery using composite microneedles for effective epicutaneous immunotherapy
Sustained antigens delivery using composite microneedles for effective epicutaneous immunotherapy
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DOI：
10.1007/s13346-023-01298-8
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发表时间：
2023-03
影响因子：
5.4
通讯作者：
Erkang Zhang;Binghui Zeng;Ruolin Song;Lu Yao;Huilian Che
中科院分区：
文献类型：
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作者：
Erkang Zhang;Binghui Zeng;Ruolin Song;Lu Yao;Huilian Che
Allergen-specific immunotherapy (SIT) is a desirable way of therapy for various allergic diseases such as food allergy (FA). However, frequent visits for more than 3 years and potential adverse effects often hinder patient compliance. Recently, many researchers started focusing on microneedles (MNs) as a new method for SIT. In this study, we proposed an implantable MNs system produced by a two-step casting process, consisting of OVA (antigen)-loaded silk microneedles and a dissolvable, flexible polyvinyl alcohol (PVA) pedestal. Different from PVA, silk fibroin hydrogel has preferable vaccine release ability in vivo and in vitro. Once MNs are inserted into the skin, the PVA pedestal can dissolve in the interstitial fluid of the excised skin within 5 min and implant the OVA-loaded silk microneedle tips in dermal layer as a sustained antigen depot, thus inducing long-lasting immune response for at least 2 weeks. After receiving 3 doses of MN-based immunotherapy, the immune response in OVA-sensitized mice was successfully suppressed, with no apparent side effects. Compared to conventional subcutaneous immunotherapy (total dose of 150g), MN immunotherapy ameliorated systemic anaphylaxis more effectively even at a lower dose (total dose of 30g), demonstrating the antigen dose-sparing potential of the proposed MNs. Moreover, due to the prolonged release effect of silk-PVA composite MNs, the frequency of immunotherapy can be significantly reduced. To sum up, through prolonged skin exposure to antigen, this implantable designed MN may offer a new therapeutic strategy for FA treatment with significant improvements in efficacy and convenience.Graphical abstractSchematic illustration of silk-PVA composite microneedles, consisting of OVA (antigen)-loaded silk microneedles and a dissolvable, flexible PVA pedestal. Once inserted into the skin, the PVA pedestal can dissolve in the interstitial fluid of the excised skin within 5 min. Subsequently, the OVA-loaded silk microneedle tips were implanted in the dermal layer as a sustained antigen depot and induced long-lasting immune response. This MNs-based immunotherapy can significantly modulate the Th1/Th2 imbalance of sensitized mice
