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具有互联多孔性的金属微针:用于生物传感和药物输送的可扩展平台。

Metallic microneedles with interconnected porosity: A scalable platform for biosensing and drug delivery.

机构信息

UCD Centre for Biomedical Engineering, School of Mechanical and Materials Engineering, University College Dublin, Belfield, Dublin 4, Ireland.

UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland; UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.

出版信息

Acta Biomater. 2018 Oct 15;80:401-411. doi: 10.1016/j.actbio.2018.09.007. Epub 2018 Sep 8.


DOI:10.1016/j.actbio.2018.09.007
PMID:30201432
Abstract

Metallic-based microneedles (MNs) offer a robust platform for minimally invasive drug delivery and biosensing applications due to their mechanical strength and proven tissue and drug compatibility. However, current designs suffer from limited functional surface area or challenges in manufacturing scalability. Here, porous 316L stainless steel MN patches are proposed. Fabricated through a scalable manufacturing process, they are suitable for storage and delivery of drugs and rapid absorption of fluids for biosensing. Fabrication of these MNs involves hot embossing a patch of stainless steel-based feedstock, sintering at 1100 °C and subsequent electropolishing. Optimisation of this manufacturing process yields devices that maintain mechanical integrity yet possess high surface area and associated porosity (36%) to maximise loading capacity. Similarly, a small pore size has been targeted (average diameter 2.22 μm, with 90% between 1.56 μm and 2.93 μm) to maximise capillarity and loading efficiency. This porous network has a theoretical wicking rate of 4.7 μl/s and can wick-up 27 ± 5 μl of fluid through capillary action which allows for absorption of pharmaceuticals for delivery. When inserted into a metabolite-loaded skin model, the MNs absorbed and recovered 17 ± 3 μl of the metabolite solution. The drug delivery performance of the porous metallic MNs (22.4 ± 4.9 µg/cm) was found to be threefold higher than that of topical administration (7.1 ± 4.3 µg/cm). The porous metallic MN patches have been shown to insert into porcine skin under a 19 N load. These results indicate the potential of design-for-manufacturing porous stainless steel MNs in biosensing and drug delivery applications. STATEMENT OF SIGNIFICANCE: Microneedles are micro-scale sharp protrusions used to bypass the stratum corneum, the skin's outer protective layer, and painlessly access dermal layers suitable for drug delivery and biosensing. Despite a depth of research in the area we have not yet seen large-scale clinical adoption of microneedle devices. Here we describe a device designed to address the potential barriers to adoption seen by other microneedles devices. We have developed a scalable, cost effective process to produce medical grade stainless steel microneedle patches which passively absorb and store drugs or interstitial fluid though a porous network and capillary action. This device, with low manufacturing and regulatory burdens may help the large-scale adoption of microneedles.

摘要

基于金属的微针 (MNs) 由于其机械强度以及经过验证的组织和药物相容性,为微创药物输送和生物传感应用提供了强大的平台。然而,目前的设计存在功能表面积有限或制造可扩展性方面的挑战。在这里,提出了多孔 316L 不锈钢 MN 贴片。通过可扩展的制造工艺制造,它们适用于药物的储存和输送以及生物传感的快速流体吸收。这些 MN 的制造涉及热压印不锈钢基底的贴片,在 1100°C 下烧结,然后进行电化学抛光。对该制造工艺进行优化可得到保持机械完整性但具有高表面积和相关孔隙率(36%)的器件,以最大限度地提高载药量。同样,已针对小孔径(平均直径 2.22μm,90%在 1.56μm 和 2.93μm 之间)进行了优化,以最大限度地提高毛细作用和载药效率。该多孔网络的理论吸液率为 4.7μl/s,可通过毛细作用吸液 27±5μl,从而允许输送药物。当插入负载有代谢物的皮肤模型中时,MNs 吸收并回收了 17±3μl 的代谢物溶液。多孔金属 MN 的药物输送性能(22.4±4.9μg/cm)是局部给药(7.1±4.3μg/cm)的三倍。已经证明多孔金属 MN 贴片可以在 19N 的负载下插入猪皮。这些结果表明,在生物传感和药物输送应用中,采用设计制造多孔不锈钢 MN 具有潜力。 意义声明:微针是用于绕过皮肤的外层保护性角质层并无痛地进入适合药物输送和生物传感的真皮层的微尺度尖锐突起。尽管在该领域进行了深入的研究,但我们尚未看到微针设备的大规模临床应用。在这里,我们描述了一种旨在解决其他微针设备采用的潜在障碍的设备。我们已经开发出一种可扩展的、具有成本效益的工艺来生产医用级不锈钢微针贴片,这些贴片通过多孔网络和毛细作用被动吸收和储存药物或间质液。这种具有低制造和监管负担的设备可能有助于大规模采用微针。

相似文献

[1]
Metallic microneedles with interconnected porosity: A scalable platform for biosensing and drug delivery.

Acta Biomater. 2018-9-8

[2]
Rapidly separating microneedles for transdermal drug delivery.

Acta Biomater. 2016-6-3

[3]
Recent advances in porous microneedles: materials, fabrication, and transdermal applications.

Drug Deliv Transl Res. 2022-2

[4]
Delivery of large molecular protein using flat and short microneedles prepared using focused ion beam (FIB) as a skin ablation tool.

Drug Deliv Transl Res. 2015-8

[5]
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Curr Drug Targets. 2014-3

[6]
Spatially controlled coating of continuous liquid interface production microneedles for transdermal protein delivery.

J Control Release. 2018-6-9

[7]
Flexible and Stretchable Microneedle Patches with Integrated Rigid Stainless Steel Microneedles for Transdermal Biointerfacing.

PLoS One. 2016-12-9

[8]
Microneedles in diagnostic, treatment and theranostics: An advancement in minimally-invasive delivery system.

Biomed Microdevices. 2021-12-8

[9]
Assessment of mechanical stability of rapidly separating microneedles for transdermal drug delivery.

Drug Deliv Transl Res. 2018-10

[10]
Toward Biofunctional Microneedles for Stimulus Responsive Drug Delivery.

Bioconjug Chem. 2015-7-15

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Drug Des Devel Ther. 2025-5-10

[2]
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Adv Sci (Weinh). 2025-6

[3]
Recent Advances in Metallic Nanostructures-assisted Biosensors for Medical Diagnosis and Therapy.

Curr Top Med Chem. 2024

[4]
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Iran J Pharm Res. 2023-5-19

[5]
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[6]
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[7]
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[8]
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Drug Deliv Transl Res. 2023-10

[9]
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[10]
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