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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：
6612948
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 2005-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6612948
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.

药物输送的最大挑战之一是以治疗速率在皮肤上施用大分子。该提案描述了使用显微针，这些针足够长，可以将药物输送到皮肤的角质层外层，但又足够短，可以避免击中神经，从而避免引起疼痛。初步研究表明，可以使用与制造集成电路相同的微加工技术从硅上蚀刻出微针阵列。这些阵列已被证明可在体外将小分子（钙黄绿素）、大分子（胰岛素、牛血清白蛋白）和纳米球（直径 100 nm）的皮肤渗透性提高多达五个数量级。初步人体研究表明，插入皮肤的微针据报道是无痛的。该工作的第一个具体目标是量化微针与皮肤的相互作用作为微针几何形状的函数。将通过体外和人体研究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以及（4）微针移除后的重新密封。研究强调定量测量和面向机制的分析。第二个具体目标是根据传输机制和微针几何形状对透皮传输进行量化和建模。将在体外研究通过扩散、对流和电泳进行的转运，并使用向无毛大鼠输送胰岛素作为模型系统进行体内验证。透皮转运的速率和分布将使用转运、微观和电测量进行实验量化，并将使用根据第一原理开发的理论模型进行分析，不涉及拟合参数。用于透皮给药的微针可以通过提供（1）无痛注射和（2）一种用户友好的方法来在数小时至数天内控制输送传统药物和大分子（例如蛋白质、DNA）等化合物，从而对医学产生重大影响。