Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies

Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies
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DOI:
10.1073/pnas.2331316100
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发表时间:
2003-11-25
影响因子:
11.1
通讯作者:
Prausnitz, MR
Prausnitz, MR
中科院分区:
综合性期刊1区
文献类型:
--
作者:
McAllister, DV;Wang, PM;Prausnitz, MR

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微米级的针阵列可以用于以微创方式在皮肤上输送药物、蛋白质和颗粒。因此,我们开发了用于硅、金属和生物可降解聚合物微针阵列的微制造技术,所述微针阵列具有实心和空心孔,所述空心和空心孔具有锥形和斜面尖端,并且特征尺寸为1至1,000 μ m。当使用固体微针时,对于半径高达50 nm的大分子和颗粒,体外皮肤渗透性增加了几个数量级。还以高效率实现了分子到活细胞中的细胞内递送。空心微针允许微升量的血液流入体内皮肤,包括微量注射胰岛素以降低糖尿病大鼠的血糖水平。
Arrays of micrometer-scale needles could be used to deliver drugs, proteins, and particles across skin in a minimally invasive manner. We therefore developed microfabrication techniques for silicon, metal, and biodegradable polymer microneedle arrays having solid and hollow bores with tapered and beveled tips and feature sizes from 1 to 1,000 pm. When solid microneedles were used, skin permeability was increased in vitro by orders of magnitude for macromolecules and particles up to 50 nm in radius. Intracellular delivery of molecules into viable cells was also achieved with high efficiency. Hollow microneedles permitted flow of microliter quantities into skin in vivo, including microinjection of insulin to reduce blood glucose levels in diabetic rats.