McCrudden Maelíosa T C, Torrisi Barbara M, Al-Zahrani Sharifah, McCrudden Cian M, Zaric Marija, Scott Christopher J, Kissenpfennig Adrien, McCarthy Helen O, Donnelly Ryan F
School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Belfast, UK.
J Pharm Pharmacol. 2015 Mar;67(3):409-25. doi: 10.1111/jphp.12248. Epub 2014 Mar 27.
We 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.
The 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).
A 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.
While 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.
我们旨在强调新型溶蚀性微针(MN)给药系统在增强经皮蛋白质递送方面的效用。疫苗接种仍然是预防传染病最被认可且有效的方法。近年来,人们对使用微创MN技术替代传统皮下疫苗注射的可能性给予了极大关注。
本研究的重点是利用微成型技术制备的由20% w/w聚(甲基乙烯基醚/马来酸)制成的溶蚀性MN阵列装置,以促进模型抗原卵清蛋白(OVA)的递送。
设计了一系列体外和体内实验,以证明负载OVA的MN阵列穿透角质层并将其有效载荷全身递送。后者通过小鼠体内体液和细胞炎症反应的激活得到证实,表现为免疫球蛋白(IgG、IgG1、IgG2a)和炎性细胞因子(特别是干扰素-γ和白细胞介素-4)的产生。重要的是,OVA掺入MN阵列后其结构完整性得以维持。
虽然需要改进制造策略以提高递送效率并减少浪费,但溶蚀性MN是“降低风险”疫苗接种和蛋白质递送策略的一个有前景的候选者。