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用于透皮递呈两亲性疫苗的溶解型微针阵列。

Dissolving Microneedle Arrays for Transdermal Delivery of Amphiphilic Vaccines.

机构信息

Department of Chemical Engineering and Materials Science, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI, 48202, USA.

Department of Oncology, Wayne State University, Detroit, MI, 48201, USA.

出版信息

Small. 2017 Jul;13(26). doi: 10.1002/smll.201700164. Epub 2017 May 19.

Abstract

Amphiphilic vaccine based on lipid-polymer conjugates is a new type of vaccine capable of self-delivering to the immune system. When injected subcutaneously, amphiphilic vaccines efficiently target antigen presenting cells in the lymph nodes (LNs) via a unique albumin-mediated transport and uptake mechanism and induce potent humoral and cellular immune responses. However, whether this new type of vaccine can be administrated via a safe, convenient microneedle-based transdermal approach remains unstudied. For such skin barrier-disruption systems, a simple application of microneedle arrays (MNs) is desired to disrupt the stratum corneum, and for rapid and pain-free self-administration of vaccines into the skin, the anatomic place permeates with an intricate mesh of lymphatic vessels draining to LNs. Here the microneedle transdermal approach is combined with amphiphilic vaccines to create a simple delivery approach which efficiently traffic molecular vaccines into lymphatics and draining LNs. The rapid release of amphiphilic vaccines into epidermis upon application of dissolving MNs to the skin of mice generates potent cellular and humoral responses, comparable or superior to those elicited by traditional needle-based immunizations. The results suggest that the amphiphilic vaccines delivered by dissolving MNs can provide a simple and safer vaccination method with enhanced vaccine efficacy.

摘要

基于脂质-聚合物缀合物的两亲疫苗是一种新型疫苗,能够自行递送至免疫系统。当皮下注射时,两亲疫苗通过独特的白蛋白介导的转运和摄取机制有效地靶向淋巴结 (LN) 中的抗原提呈细胞,并诱导强烈的体液和细胞免疫应答。然而,这种新型疫苗是否可以通过安全、方便的基于微针的经皮途径给药仍未得到研究。对于这种皮肤屏障破坏系统,希望通过简单地应用微针阵列 (MN) 来破坏角质层,并且为了快速无痛地将疫苗自行注入皮肤,解剖位置渗透着错综复杂的淋巴管网络,这些淋巴管通向 LN。在这里,微针经皮给药途径与两亲疫苗相结合,创造了一种简单的给药方法,可有效地将分子疫苗输送至淋巴管和引流的 LN 中。当将溶解的 MN 应用于小鼠的皮肤时,两亲疫苗迅速释放到表皮中,引发强烈的细胞和体液反应,与传统的基于针的免疫接种相当或更优。结果表明,溶解的 MN 递送的两亲疫苗可以提供一种简单且更安全的疫苗接种方法,增强疫苗的功效。

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