Dissolving undercut microneedle arrays for multicomponent cutaneous vaccination.
Dissolving undercut microneedle arrays for multicomponent cutaneous vaccination.
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DOI：
10.1016/j.jconrel.2019.11.023
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发表时间：
2020-01-10
期刊：
影响因子：
--
通讯作者：
Falo LD Jr
中科院分区：
文献类型：
--
作者：
Balmert SC;Carey CD;Falo GD;Sethi SK;Erdos G;Korkmaz E;Falo LD Jr
皮肤是疫苗接种的有吸引力的组织靶点，因为它容易接近并含有密集的抗原呈递细胞和免疫辅助细胞。微针阵列（MNAs）正在成为一种有效的工具，原位工程的皮肤微环境，使不同的免疫策略。在这里，我们提出了新的溶解底切MNAs，并证明其应用于有效的多组分皮肤接种。MNAs由微米级针头组成，其锥形针头由底切杆区域支撑，底部有圆角，以确保在应用过程中成功穿透皮肤并保持。先前制造溶解底切微结构的努力是有限的，并且需要复杂且冗长的加工和组装步骤。在目前的研究中，我们战略性地将联合收割机三维（3D）激光光刻（一种具有独特几何能力和纳米级分辨率的新兴微增材制造方法）与有利材料的微成型相结合。这种方法使得能够用底切微针可再现地生产溶解的MNA，所述底切微针可以尖端装载多种生物货物，例如抗原（卵清蛋白）和佐剂（Poly（I：C））。所得到的MNA满足几何（即，尖锐的尖端和光滑的边缘）和机械强度要求，以无故障地穿透人和鼠皮肤，从而同时将多组分（抗原加佐剂）疫苗递送到相同的皮肤微环境。使用这些MNAs的小鼠皮肤接种诱导比传统肌内注射引起的更有效的抗原特异性细胞和体液免疫应答。总之，这些底切MNAs的独特几何特征和与多种药物和生物制剂相容的相关制造策略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。
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 (i.e., 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.
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影响因子：
82.9
作者：
Condon, C;Watkins, SC;Falo, LD
通讯作者：
Falo, LD
影响因子：
10
作者：
DeMuth, Peter C.;Min, Younjin;Irvine, Darrell J.;Hammond, Paula T.
通讯作者：
Hammond, Paula T.
DOI：
10.1016/j.jconrel.2010.10.033
发表时间：
2011-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Chu LY;Prausnitz MR
通讯作者：
Prausnitz MR
影响因子：
10.8
作者：
Ding, Z.;Verbaan, F. J.;Bouwstra, J. A.
通讯作者：
Bouwstra, J. A.
影响因子：
3.7
作者：
Johnson, Ashley R.;Procopio, Adam T.
通讯作者：
Procopio, Adam T.