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首页> 外文期刊>Journal of Controlled Release: Official Journal of the Controlled Release Society >Dissolving undercut microneedle arrays for multicomponent cutaneous vaccination
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Dissolving undercut microneedle arrays for multicomponent cutaneous vaccination

机译：溶解底切微针阵列以进行多组分皮肤疫苗接种

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摘要

The skin is an attractive tissue target for vaccination, as it is readily accessible and contains a dense population of antigen-presenting and immune-accessory cells. Microneedle arrays (MNAs) are emerging as an effective tool for in situ engineering of the cutaneous microenvironment to enable diverse immunization strategies. Here, we present novel dissolving undercut MNAs and demonstrate their application for effective multicomponent cutaneous vaccination. The MNAs are composed of micron-scale needles featuring pyramidal heads supported by undercut stem regions with filleted bases to ensure successful skin penetration and retention during application. Prior efforts to fabricate dissolving undercut microstructures were limited and required complex and lengthy processing and assembly steps. In the current study, we strategically combine three-dimensional (3D) laser lithography, an emerging micro-additive manufacturing method with unique geometric capabilities and nanoscale resolution, and micromolding with favorable materials. This approach enables reproducible production of dissolving MNAs with undercut microneedles that can be tip-loaded with multiple biocargos, such as antigen (ovalbumin) and adjuvant (Poly(I:C)). The resulting MNAs fulfill the geometric (sharp tips and smooth edges) and mechanical-strength requirements for failure-free penetration of human and murine skin to simultaneously deliver multicomponent (antigen plus adjuvant) vaccines to the same cutaneous microenvironment. Cutaneous vaccination of mice using these MNAs induces more potent antigen-specific cellular and humoral immune responses than those elicited by traditional intramuscular injection. Together, the unique geometric features of these undercut MNAs and the associated manufacturing strategy, which is compatible with diverse drugs and biologics, could enable a broad range of non-cutaneous and cutaneous drug delivery applications, including multicomponent vaccination.
机译：皮肤是疫苗接种的有吸引力的组织靶标，因为它易于接近并且含有浓密的抗原呈递和免疫辅助细胞。 Microneedle阵列（MNAS）是作为一种有效的皮肤微环境工程工具，以实现各种免疫策略。在这里，我们提出了新型溶解的底切MNA，并证明了它们用于有效的多组分皮肤接种的应用。 MNA由微米级针组成，该针头具有由底切干区域支撑的金字塔顶头，其中底座底座，以确保在施用期间成功的皮肤穿透和保留。在制造溶解的沉积微观结构的情况下努力是有限的，需要复合和冗长的加工和装配步骤。在目前的研究中，我们战略性地结合了三维（3D）激光光刻，具有独特的几何能力和纳米级分辨率的新出现的微观添加剂制造方法，以及具有良好材料的微胶体。该方法使得能够使用底切微针的溶解MNA的可再现产生，其可以用多种生物戒指（例如抗原（卵烧）和佐剂（Poly（I：C））倾斜。所得到的MNA满足了几何（尖锐的尖端和光滑边缘）和机械强度要求，以便无失败的人和鼠皮肤的失败渗透，同时将多组分（抗原加佐剂）疫苗递送至同一皮肤微环境。使用这些MNA的小鼠的皮肤接种诱导更有效的抗原特异性细胞和体液免疫应答，而不是传统的肌肉注射引发的细胞和体液免疫应答。这些底切MNA的独特的几何特征在一起和相关的制造策略与不同的药物和生物学相容，可以实现广泛的非皮肤和皮肤药物递送应用，包括多组分疫苗接种。

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