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无洁净室环境下制造用于多模式药物输送的微针

Cleanroom-Free Fabrication of Microneedles for Multimodal Drug Delivery.

机构信息

Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT, 06030, USA.

Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA.

出版信息

Small. 2023 Jul;19(29):e2207131. doi: 10.1002/smll.202207131. Epub 2023 Apr 7.

Abstract

Microneedles have recently emerged as a powerful tool for minimally invasive drug delivery and body fluid sampling. To date, high-resolution fabrication of microneedle arrays (MNAs) is mostly achieved by the utilization of sophisticated facilities and expertise. Particularly, hollow microneedles have usually been manufactured in cleanrooms out of silicon, resin, or metallic materials. Such strategies do not support the fabrication of microneedles from biocompatible/biodegradable materials and limit the capability of multimodal drug delivery for the controlled release of different therapeutics through a combination of injection and sustained diffusion. This study implements low-cost 3D printers to fabricate relatively large needle arrays, followed by repeatable shrink-molding of hydrogels to form high-resolution molds for solid and hollow MNAs with controllable sizes. The developed strategy further enables modulating surface topography of MNAs to tailor their surface area and instantaneous wettability for controllable drug delivery and body fluid sampling. Hybrid gelatin methacryloyl (GelMA)/polyethylene glycol diacrylate (PEGDA) MNAs are fabricated using the developed strategy that can easily penetrate the skin and enable multimodal drug delivery. The proposed method holds promise for affordable, controllable, and scalable fabrication of MNAs by researchers and clinicians for controlled spatiotemporal administration of therapeutics and sample collection.

摘要

微针最近成为一种用于微创药物输送和体液采样的强大工具。迄今为止,微针阵列(MNAs)的高分辨率制造主要通过利用复杂的设备和专业知识来实现。特别是,空心微针通常是在洁净室中由硅、树脂或金属材料制造的。这些策略不支持使用生物相容性/可生物降解材料制造微针,并且限制了通过注射和持续扩散相结合来控制不同治疗药物的释放的多模式药物输送的能力。本研究利用低成本 3D 打印机制造相对较大的针阵列,然后对水凝胶进行可重复的收缩成型,以形成具有可控尺寸的固体和空心 MNAs 的高分辨率模具。所开发的策略进一步实现了调制 MNAs 的表面形貌,以调整其表面积和瞬时润湿性,从而实现可控的药物输送和体液采样。使用所开发的策略制造了混合明胶甲基丙烯酰(GelMA)/聚乙二醇二丙烯酸酯(PEGDA)微针,这些微针可以轻松穿透皮肤并实现多模式药物输送。该方法有望为研究人员和临床医生提供负担得起、可控和可扩展的 MNAs 制造,以实现治疗药物的时空控制给药和样本采集。

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