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氙化二氟化物干法刻蚀在固体微针微纳制造中的应用:经皮给药的潜在策略。

Xenon Difluoride Dry Etching for the Microfabrication of Solid Microneedles as a Potential Strategy in Transdermal Drug Delivery.

机构信息

UNAM-National Nanotechnology Research Center, Bilkent University, Ankara, 06800, Turkey.

Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, 06800, Turkey.

出版信息

Small. 2023 Jul;19(27):e2206510. doi: 10.1002/smll.202206510. Epub 2023 Mar 16.

DOI:10.1002/smll.202206510
PMID:36929149
Abstract

Although hypodermic needles are a "gold standard" for transdermal drug delivery (TDD), microneedle (MN)-mediated TDD denotes an unconventional approach in which drug compounds are delivered via micron-size needles. Herein, an isotropic XeF dry etching process is explored to fabricate silicon-based solid MNs. A photolithographic process, including mask writing, UV exposure, and dry etching with XeF is employed, and the MN fabrication is successfully customized by modifying the CAD designs, photolithographic process, and etching conditions. This study enables fabrication of a very dense MNs (up to 1452 MNs cm ) with height varying between 80 and 300 µm. Geometrical features are also assessed using scanning electron microscopy (SEM) and 3D laser scanning microscope. Roughness of the MNs are improved from 0.71 to 0.35 µm after titanium and chromium coating. Mechanical failure test is conducted using dynamic mechanical analyzer to determine displacement and stress/strain values. The coated MNs are subjected to less displacement (≈15 µm) upon the applied force. COMSOL Multiphysics analysis indicates that MNs are safe to use in real-life applications with no fracture. This technique also enables the production of MNs with distinct shape and dimensions. The optimized process provides a wide range of solid MN types to be utilized for epidermis targeting.

摘要

尽管皮下注射器是经皮药物输送(TDD)的“金标准”,但微针(MN)介导的 TDD 表示一种非传统的方法,其中药物化合物通过微米大小的针输送。在此,探索了各向同性 XeF 干法刻蚀工艺来制造基于硅的固体 MN。采用光刻工艺,包括掩模写入、UV 曝光和 XeF 干法刻蚀,通过修改 CAD 设计、光刻工艺和蚀刻条件成功定制 MN 制造。本研究能够制造非常密集的 MN(最高可达 1452 MNs cm ),高度在 80 至 300 µm 之间变化。还使用扫描电子显微镜(SEM)和 3D 激光扫描显微镜评估了几何特征。在涂覆钛和铬后,MN 的粗糙度从 0.71 µm 提高到 0.35 µm。使用动态机械分析仪进行机械失效测试,以确定位移和应力/应变值。在施加力时,涂覆的 MN 的位移较小(≈15 µm)。COMSOL Multiphysics 分析表明,MN 在实际应用中使用是安全的,不会发生断裂。该技术还能够生产具有不同形状和尺寸的 MN。优化后的工艺为表皮靶向提供了广泛的固体 MN 类型。

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