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MICROFABRICATED MICRONEEDLES FOR DRUG DELIVERY

用于药物输送的微型微针

基本信息

批准号：
6387014
负责人：
MARK R. PRAUSNITZ
金额：
$ 18.54万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-07-01 至 2004-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6387014
关键词：
biomedical equipment development clinical biomedical equipment clinical research consumable /disposable biomedical equipment drug delivery systems human subject hypodermic needle laboratory rat postmortem

项目摘要

One of the greatest challenges in drug delivery is the administration of macromolecules across the skin at therapeutic rates. This proposal describes the use of microscopic needles which are long enough to deliver drugs across the skin's outer layer of stratum corneum, but are short enough to avoid hitting nerves and thereby avoid causing pain. Preliminary studies show that arrays of microneedles can be etched from silicon using the same microfabrication technology used to made integrated circuits. These arrays have been shown to increase skin permeability in vitro by up to five orders of magnitude for small molecules (calcein), macromolecules (insulin, bovine serum albumin) and nanospheres (100 nm diameter). Preliminary human studies indicate that microneedles inserted into the skin are reported as painless. The first specific aim of the proposed work addresses quantifying the microneedle-skin interaction as a function of microneedle geometry. The effects of six geometrical features will be considered through in vitro and human studies to measure the (1) force for microneedle insertion, (2) pain caused by microneedles, (3) skin irritation caused by microneedles and (4) resealing after microneedles are removed. Studies emphasize quantitative measurements and mechanism-oriented analysis. The second specific aim addresses quantifying and modeling transdermal transport as a function of transport mechanisms and microneedle geometry. Transport by diffusion, convection and electrophoresis will be studied in vitro, with in vivo validation using delivery of insulin to hairless rats as a model system. Rates and distribution of transdermal transport will be quantified experimentally using transport, microscopic and electrical measurements and will be analyzed using a theoretical model developed from first principles and involving no fitted parameters. Microneedles for transdermal drug delivery could significantly impact medicine by providing (1) painless injections and (2) a user-friendly method for controlled delivery of compounds such as conventional drugs and macromolecules (e.g., proteins, DNA) over hours to days.

药物输送中最大的挑战之一是以治疗率在皮肤上给药。这项建议描述了使用显微针头，这种针头足够长，可以将药物输送到皮肤角质层的外层，但又足够短，可以避免撞击神经，从而避免引起疼痛。初步研究表明，微针阵列可以使用与制造集成电路相同的微制造技术从硅中蚀刻出来。这些阵列已被证明可以增加小分子(钙黄绿素)、大分子(胰岛素、牛血清白蛋白)和纳米球(直径100 nm)的体外皮肤渗透性高达五个数量级。初步的人体研究表明，插入皮肤的微针据报道是无痛的。拟议工作的第一个具体目标是将微针与皮肤的相互作用量化为微针几何形状的函数。通过体外和人体研究，将考虑六个几何特征的影响，以测量(1)微针插入的力，(2)微针引起的疼痛，(3)微针引起的皮肤刺激，(4)微针取出后的再密封。研究强调定量测量和机制导向分析。第二个具体目标是量化和模拟作为传输机制和微针几何形状的经皮传输。将在体外研究通过扩散、对流和电泳法进行的转运，并以无毛大鼠体内胰岛素输送为模型系统进行体内验证。透皮传输的速率和分布将使用传输、显微和电学测量进行实验量化，并将使用根据第一原理开发的不包含拟合参数的理论模型进行分析。用于经皮给药的微针可以提供(1)无痛注射和(2)用户友好的方法，在几个小时到几天的时间内控制诸如传统药物和大分子(例如蛋白质、DNA)的药物输送，从而显著影响药物。