Laser-engineered dissolving microneedle arrays for protein delivery: potential for enhanced intradermal vaccination

Laser-engineered dissolving microneedle arrays for protein delivery: potential for enhanced intradermal vaccination
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DOI:
10.1111/jphp.12248
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发表时间:
2015-03-01
影响因子:
3.3
通讯作者:
Donnelly, Ryan F.
Donnelly, Ryan F.
中科院分区:
医学3区
文献类型:
--
作者:
McCrudden, Maelosa T. C.;Torrisi, Barbara M.;Donnelly, Ryan F.

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目的:我们的目的是强调新的溶解微针(MN)为基础的传递系统,以增强蛋白质的透皮给药的实用性。接种疫苗仍然是预防传染病最被接受和最有效的方法。近年来,人们对使用微创MN技术替代传统皮下注射疫苗的可能性产生了极大的兴趣。方法本研究的重点是利用由20%w/w聚乙烯制成的溶解MN阵列器件(甲基乙烯基醚/马来酸),用于促进模型抗原的递送,关键发现设计了一系列体外和体内实验以证明负载有OVA的MN阵列穿透角质层并全身递送其有效载荷。后者通过小鼠体液和细胞炎症反应的激活来证明,这通过免疫球蛋白(IgG、IgG 1、IgG 2a)和炎性细胞因子(特别是干扰素-γ和白细胞介素-4)的产生来表示。重要的是,纳入MN arrays后的OVA的结构完整性maintained.ConclusionWhile增强的制造策略,需要提高交付效率和减少浪费,溶解MN是一个有前途的候选人降低风险的疫苗接种和蛋白质交付策略。
ObjectivesWe aimed to highlight the utility of novel dissolving microneedle (MN)-based delivery systems for enhanced transdermal protein delivery. Vaccination remains the most accepted and effective approach in offering protection from infectious diseases. In recent years, much interest has focused on the possibility of using minimally invasive MN technologies to replace conventional hypodermic vaccine injections.MethodsThe focus of this study was exploitation of dissolving MN array devices fabricated from 20% w/w poly(methyl vinyl ether/maleic acid) using a micromoulding technique, for the facilitated delivery of a model antigen, ovalbumin (OVA).Key findingsA series of in-vitro and in-vivo experiments were designed to demonstrate that MN arrays loaded with OVA penetrated the stratum corneum and delivered their payload systemically. The latter was evidenced by the activation of both humoral and cellular inflammatory responses in mice, indicated by the production of immunoglobulins (IgG, IgG1, IgG2a) and inflammatory cytokines, specifically interferon-gamma and interleukin-4. Importantly, the structural integrity of the OVA following incorporation into the MN arrays was maintained.ConclusionWhile enhanced manufacturing strategies are required to improve delivery efficiency and reduce waste, dissolving MN are a promising candidate for reduced-risk' vaccination and protein delivery strategies.