ACOUSTICALLY ACTIVATED MICELLAR DRUG DELIVERY

声学激活胶束药物输送

• 批准号: 2741630
• 负责人: NATALYA Y RAPOPORT
• 金额: $ 24.67万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-15 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2741630
• 关键词: antineoplastics; apoptosis; daunorubicin; doxorubicin; drug delivery systems; drug vehicle; electron spin resonance spectroscopy; fluorescence spectrometry; hyperthermia; micelles; multidrug resistance; neoplasm /cancer chemotherapy; pharmacokinetics; technology /technique development; tissue /cell culture; ultrasound

DESCRIPTION(Adapted from Applicant's Abstract): Chemotherapy for localized tumor treatment often is administered systemically, which delivers the chemotherapeutic agents throughout the body (as well as to the target sites), and can often cause unwanted side effects on other tissues in the body. An ideal scenario for localized delivery of therapeutic agents would be to sequester the drug in a package that would have minimal interaction with the body, and would contain the drug until release; then at the appropriate time and place in the body the drug could be released from the sequestering container. The main thrust of the proposed research is to combine the advantages of ultrasonic enhancement of drug transport and of micellar drug carrier into a novel technology which will deliver drugs predominantly to tissues exposed to localized acoustic energy. Ultrasound has many advantages as a mediator of drug delivery: the technique is non-invasive; it can be carefully controlled and focused on the target tissue; ultrasound appears to "activate," or to enhance the pharmacological activity of some drugs; it enhances drug transport through tissues and across cell membranes; and it can simultaneously create a hyperthermic condition which can enhance the destruction of cancerous tissues. Micellar drug carriers are advantageous because they encapsulate chemotherapeutic agents thus reducing the systemic concentration of the free drug and preventing unwanted drug interaction with healthy cells. The foundation of this proposal is our finding that ultrasound can enhance drug uptake by tumor cells when drug is delivered from micellar carriers. There are numerous potential advantages of the proposed technology over the state-of-the-art technologies: 1) long-circulating micelles will be used to encapsulate drug and reduce the systemic concentrations of free drug, thus reducing drug toxicity; 2) drug can be released in a controlled and localized volume by focusing acoustic energy on the volume; 3) the timing of drug release can be controlled; 4) the micelles will provide for the re-encapsulation of the drug outside of the localized target volume; 5) application of acoustic energy for enhancing drug uptake has additional benefit of hyperthermic therapy and acoustic potentialization of the drug; 6) ultrasound can penetrate to deep tissues, which most current techniques cannot provide.

描述（改编自申请人的摘要）：局部化学疗法 肿瘤治疗通常是系统地给药的，这提供了 整个身体（以及目标部位）的化学治疗剂， 并且通常会对体内其他组织产生不良的副作用。一个 用于局部交付治疗剂的理想情况是 将药物隔离在一个包装中，该包装与与 身体，将包含该药物，直到释放为止；然后在适当的时间 并放在体内该药物可以从隔离中释放 容器。 拟议研究的主要目的是结合 超声波运输和胶束药物载体的超声增强 新技术将主要将药物运送到暴露于组织的组织 局部声能。超声是药物中介的许多优势 交付：该技术是无创的；它可以仔细控制，并且 专注于目标组织；超声似乎“激活”或增强 某些药物的药理活性；它增强了通过 组织和跨细胞膜；它可以同时创建一个 高温状态，可以增强癌组织的破坏。 胶束药物载体很有利，因为它们封装了 化学治疗剂因此降低了游离的全身浓度 药物并防止不必要的药物与健康细胞的相互作用。这 该提议的基础是我们发现超声可以增强药物 从胶束载体中输送药物时，肿瘤细胞的吸收。 拟议技术比 最先进的技术：1）长循环胶束将用于 封装药物并降低自由药物的全身浓度，因此 降低药物毒性； 2）可以在受控和局部释放药物 通过将声能集中在体积上来体积； 3）药物释放的时间 可以控制； 4）胶束将提供重新包裹 在局部目标量之外的药物； 5）使用声能 为了增强药物摄取，高温疗法和 药物的声学潜在化； 6）超声可以渗透到深处 组织，大多数当前技术无法提供的组织。