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通过光掩膜直接制造微针阵列以透过皮肤递送胶原蛋白。

Direct microneedle array fabrication off a photomask to deliver collagen through skin.

作者信息

Kochhar Jaspreet Singh, Anbalagan Parthiban, Shelar Sandeep Balu, Neo Jun Kai, Iliescu Ciprian, Kang Lifeng

机构信息

Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore.

出版信息

Pharm Res. 2014 Jul;31(7):1724-34. doi: 10.1007/s11095-013-1275-1. Epub 2014 Jan 22.

Abstract

PURPOSE

To fabricate microneedle arrays directly off a photomask using a simple photolithographical approach and evaluate their potential for delivering collagen.

METHODS

A simple photolithographical approach was developed by using photomask consisting of embedded micro-lenses that govern microneedle geometry in a mould free process. Microneedle length was controlled by use of simple glass scaffolds as well as addition of backing layer. The fabricated arrays were tested for their mechanical properties by using a force gauge as well as insertion into human skin with trypan blue staining. Microneedle arrays were then evaluated for the delivery of fluorescent collagen, which was evaluated using a confocal laser scanning microscope.

RESULTS

Microneedles with sharp tips ranging between 41.5 ± 8.4 μm and 71.6 ± 13.7 μm as well as of two different lengths of 1336 ± 193 μm and 957 ± 171 μm were fabricated by using the photomasks. The microneedles were robust and resisted fracture forces up to 25 N. They were also shown to penetrate cadaver human skin samples with ease; especially microneedle arrays with shorter length of 957 μm penetrated up to 72% of needles. The needles were shown to enhance permeation of collagen through cadaver rat skin, as compared to passive diffusion of collagen.

CONCLUSIONS

A simple and mould free approach of fabricating polymeric microneedle array is proposed. The fabricated microneedle arrays enhance collagen permeation through skin.

摘要

目的

采用简单的光刻方法直接在光掩模上制备微针阵列,并评估其递送胶原蛋白的潜力。

方法

开发了一种简单的光刻方法,使用由嵌入式微透镜组成的光掩模,在无模具工艺中控制微针的几何形状。通过使用简单的玻璃支架以及添加背衬层来控制微针长度。使用测力计测试制备的阵列的机械性能,并将其插入经台盼蓝染色的人体皮肤中。然后评估微针阵列对荧光胶原蛋白的递送情况,使用共聚焦激光扫描显微镜进行评估。

结果

使用光掩模制备出了尖端尖锐、长度在41.5±8.4μm至71.6±13.7μm之间,以及两种不同长度分别为1336±193μm和957±171μm的微针。这些微针坚固耐用,能承受高达25N的断裂力。它们还被证明能轻松穿透尸体人体皮肤样本;特别是长度为957μm的较短微针阵列,高达72%的针能够穿透。与胶原蛋白的被动扩散相比,这些针被证明能增强胶原蛋白透过尸体大鼠皮肤的渗透。

结论

提出了一种简单且无模具的制备聚合物微针阵列的方法。制备的微针阵列增强了胶原蛋白透过皮肤的渗透。

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