MICROFABRICATED MICRONEEDLES FOR DRUG DELIVERY

用于药物输送的微型微针

• 批准号: 6086000
• 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
• 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/6086000
• 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

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.

药物递送中的最大挑战之一是以治疗速率通过皮肤施用大分子。 该提案描述了使用显微针头，其足够长以将药物输送穿过皮肤的角质层外层，但足够短以避免触及神经，从而避免引起疼痛。 初步研究表明，微针阵列可以从硅蚀刻使用相同的微细加工技术用于制造集成电路。 这些阵列已被证明在体外增加皮肤渗透性高达五个数量级的小分子（钙黄绿素），大分子（胰岛素，牛血清白蛋白）和纳米球（100纳米直径）。 初步的人体研究表明，据报道，插入皮肤的微针是无痛的。 所提出的工作的第一个具体目标解决了作为微针几何形状的函数的微针-皮肤相互作用的量化。 将通过体外和人体研究考虑六种几何特征的影响，以测量（1）微针插入力，（2）微针引起的疼痛，（3）微针引起的皮肤刺激和（4）移除微针后的重新密封。 研究强调定量测量和面向机制的分析。 第二个具体目标解决了作为传输机制和微针几何形状的函数的经皮传输的量化和建模。 将在体外研究通过扩散、对流和电泳进行的转运，并使用无毛大鼠作为模型系统进行胰岛素递送的体内验证。经皮转运的速率和分布将使用转运、显微镜和电学测量进行实验量化，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。 用于透皮药物递送的针头可以通过提供（1）无痛注射和（2）用于控制递送化合物如常规药物和大分子（例如，蛋白质、DNA）持续数小时至数天。