Engineering Non-Polymer-Based Drug-Release Surface for Biomedical Devices

用于生物医学器械的非聚合物药物释放表面工程

• 批准号: 7343107
• 负责人: Dave M Johnson
• 金额: $ 36.13万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7343107
• 关键词: Acids; Acute; Address; Adverse effects; Alcohols; Area; Binding; Biomedical Engineering; Cessation of life; Chemicals; Chemistry; Condition; Coronary; Coupling; Devices; Dexamethasone; Dose; Drug usage; Engineering; Environment; Equipment; Esters; Goals; Housing; Hybrids; Implant; In Vitro; Kinetics; Medicine; Metals; Methods; Modification; Molecular; Nanotechnology; Operative Surgical Procedures; Oryctolagus cuniculus; Paclitaxel; Pharmaceutical Preparations; Physiological; Polymers; Prevalence; Protocols documentation; Rate; Reaction; Research; Scanning Tunneling Microscopy; Sirolimus; Site; Spectrum Analysis; Stainless Steel; Stents; Structure of molecular layer of cerebellar cortex; Surface; Techniques; Technology; Texas; Therapeutic; Titanium; Universities; Water; Week; Work; X ray microscopy; base; chemical synthesis; density; design; implant coating; implantation; in vivo; isobutylene; medical implant; monolayer; nanoscience; programs; research study; restenosis; success; titanium dioxide

DESCRIPTION (provided by applicant): The use of a surgical implant often requires the administration of one or more drugs to increase the success of the surgery. The modification of implants to deliver the drug directly to the site of the surgery offers the promise of minimizing the drug dose needed, while maximizing the therapeutic benefit. Our long-term goal is to develop an advanced strategy for drug release from implants. The central hypothesis is that drugs may be attached to the surface through the use of a highly ordered molecular coating called a self-assembled monolayer (SAM) and subsequently released at a controlled rate. The rationale for this research is that drug-modified SAMs (DSAMs) will have therapeutic benefit which can enhance the value of any surgical implant. The initial target for implant modification is the coronary arterial stent, which has a strong need for a DSAM due to the prevalence of restenosis (arterial re-narrowing) as a post-surgical problem and complications resulting from polymer-based coatings. Specifically, the research objective proposed herein will focus on developing and optimizing DSAMs for coronary stents which deliver anti-restenotic drugs such as paclitaxel, sirolimus (rapamycin) or dexamethasone. This application is of acute urgency as complications from polymer-based coatings have been implicated in deaths. The specific aims for this project are: (1) to develop methods to maximize the amount of drug loaded onto a metal surface through the use of DSAMs; (2) to optimize release rates of drugs present at surfaces; and (3) to adapt techniques to nanoporous surfaces. These specific aims will be accomplished by a multifaceted program including chemical synthesis, surface studies, and drug release studies. This research offers the potential to modify any currently designed medical implant to deliver a drug directly to the site of the implantation surgery. This will result in implants that have additional therapeutic benefit and fewer side effects from surgery.

描述（由申请人提供）：使用手术植入物通常需要使用一种或多种药物来增加手术的成功。植入物直接将药物运送到手术部位的修饰提供了最大程度地减少所需药物剂量的承诺，同时最大程度地提高治疗益处。我们的长期目标是制定从植入物中释放药物的先进策略。中心假设是，可以通过使用称为自组装单层（SAM）的高度有序的分子涂层将药物连接到表面上，并随后以受控速率释放。这项研究的理由是，药物修饰的SAMS（DSAMS）将具有治疗益处，从而可以增强任何手术植入物的价值。植入物修饰的最初靶标是冠状动脉支架，由于再狭窄（动脉重新结核）作为手术后问题和由聚合物基于聚合物的涂料引起的并发症，因此对DSAM非常需要DSAM。具体而言，本文提出的研究目标将着重于开发和优化冠状动脉支架的DSAM，这些冠状动脉支架提供抗雷神药物，例如紫杉醇，西洛洛里木斯（Rapamycin）或地塞米松。由于基于聚合物的涂料的并发症已与死亡有关，因此这种应用是急性的。该项目的具体目的是：（1）开发方法，通过使用DSAM最大化金属表面上的药物量； （2）优化在表面上存在的药物的释放率； （3）将技术适应纳米孔表面。这些具体目标将通过一个多面计划来实现，包括化学合成，表面研究和药物释放研究。 这项研究提供了修改当前设计的医学植入物，以直接将药物直接运送到植入手术部位。这将导致植入物具有额外的治疗益处，而手术的副作用较少。