Biodegradable polymer microneedles: Fabrication, mechanics and transdermal drug delivery
Biodegradable polymer microneedles: Fabrication, mechanics and transdermal drug delivery
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DOI：
10.1016/j.jconrel.2005.02.002
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发表时间：
2005-05-05
影响因子：
10.8
通讯作者：
Prausnitz, MR
中科院分区：
文献类型：
--
作者：
Park, JH;Allen, MG;Prausnitz, MR
为克服皮肤阻碍大多数药物经皮传递的屏障特性，主要由硅或金属制成的微针阵列已被微加工出来。本研究涉及由生物相容性和生物可降解聚合物制成的微针，预计这些微针将提高安全性和可制造性。为了制造具有尖锐针尖的生物可降解聚合物微针，采用了微机电掩模和蚀刻技术来制造斜角针尖和凿形针尖微针，并开发了一种新的制造方法，利用基于原位透镜的光刻方法来制造锥形针尖微针。为了复制微加工的母结构，制作了聚二甲基硅氧烷（PDMS）微模具，并开发了一种基于真空的新方法，用聚乳酸、聚乙醇酸及其共聚物填充模具。对制成的微针进行的力学测试测量了轴向加载时微针断裂的力，发现这种破坏力随材料的杨氏模量和微针底部直径的增加而增加，随微针长度的增加而减小。破坏力通常远大于将微针插入皮肤所需的力，这表明生物可降解聚合物可具有满足微针要求的令人满意的力学性能。最后，聚合物微针阵列被证明可使人尸体皮肤对一种低分子量示踪剂（钙黄绿素）和一种大分子蛋白质（牛血清白蛋白）的渗透性提高多达三个数量级。总之，这些结果表明，生物可降解聚合物微针可以被制造成具有合适的几何形状和足够的强度以插入皮肤，从而显著提高分子的经皮运输。（c）2005爱思唯尔公司。版权所有。
To overcome the skin's barrier properties that block transdermal delivery of most drugs, arrays of microscopic needles have been microfabricated primarily out of silicon or metal. This study addresses microneedles made of biocompatible and biodegradable polymers, which are expected to improve safety and manufacturability. To make biodegradable polymer microneedles with sharp tips, micro-electromechanical masking and etching were adapted to produce beveled- and chisel-tip microneedles and a new fabrication method was developed to produce tapered-cone microneedles using an in situ lens-based lithographic approach. To replicate microfabricated master structures, PDMS micromolds were generated and a novel vacuum-based method was developed to fill the molds with polylactic acid, polyglycolic acid, and their co-polymers. Mechanical testing of the resulting needles measured the force at which needles broke during axial loading and found that this failure force increased with Young's modulus of the material and needle base diameter and decreased with needle length. Failure forces were generally much larger than the forces needed to insert microneedles into skin, indicating that biodegradable polymers can have satisfactory mechanical properties for microneedles. Finally, arrays of polymer microneedles were shown to increase permeability of human cadaver skin to a low-molecular weight tracer, calcein, and a macromolecular protein, bovine serum albumin, by up to three orders of magnitude. Altogether, these results indicate that biodegradable polymer microneedles can be fabricated with an appropriate geometry and sufficient strength to insert into skin, and thereby dramatically increase transdermal transport of molecules. (c) 2005 Elsevier B.V. All rights reserved.