Acoustically Activated Micellar Drug Delivery

声激活胶束药物输送

• 批准号: 6757239
• 负责人: NATALYA Y RAPOPORT
• 金额: $ 28.19万
• 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 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6757239
• 关键词: Acoustically; Activated; Micellar; Drug; Delivery

DESCRIPTION (provided by applicant): The main thrust of the proposed research is to combine the advantages of ultrasonic drug delivery and micellar drug carriers into a novel technology that will deliver high local concentrations of drugs to tissues exposed to localized acoustic energy. Ultrasound is non-invasive, can be carefully controlled and focused on the target tissue; it induces drug release from micelles and enhances the intracellular drug uptake and it can simultaneously create a hyperthermic condition. Micellar drug carriers prevent unwanted drug interaction with healthy tissues while sensitizing multidrug resistant (MDR) cells to the action of drugs. The foundation of this proposal is the hypothesis that micellar drug delivery combined lwith ultrasonic activation can target drugs to tumors, enhance the cytotoxicity of drugs in sensitive and MDR tumors, and suppress tumor growth. Specific aims of the project include: 1. To extend a panel of /cell fines, drugs, and polymeric micelles for which the above technology may prove beneficial, In particular, to include taxol into the panel of drugs since it has low solubility in commonly used media and low activity in multidrug resistant cells. The cytotoxicity of Doxorubicin (DOX) and taxol in vitro will be measured in A2780 ovarian carcinoma, MCF7 breast cancer, and P388 leukemia cell lines (both dwg-sensitive and MDR), and in DHD/KlZ/TRb colon cancer cell line. 2. To test the hypothesis that micelfar drug delivery combined with ultrasound suppresses tumor growth in vivo and increases survival rates of tumor-bearing mice. Experiments will be performed with drug-sensitive and MDR A2780 and MCF7 tumors grown subcutaneously, and P388 internal tumors grown in the peritoneal cavity of mice; micellar-encapsutated DOX and taxol will be delivered with and without 20-kHz ultrasound applied to the tumors at various duty cycles and power densities. 3. To extend and scale up in vivo experiments using the DHDMZFRb colon cancer model in rats. Experiments will be performed with micellar encapsulated DOX combined with 20-kHz and 70-kHz ultrasound. All three specific aims are focused on clinically relevant targets.

描述（由申请人提供）：拟议的研究的主要目的是将超声药物递送和胶束药物载体的优势结合到一种新型技术中，将局部浓度高的药物提供给暴露于局部声学能量的组织。超声是无创的，可以仔细控制并专注于目标组织。它诱导药物从胶束中释放并增强细胞内药物的摄取，并可以同时产生过度热的疾病。胶束药物载体可以防止不必要的药物与健康组织的相互作用，同时使多药耐药（MDR）细胞对药物的作用敏感。该提案的基础是假设，胶束药物递送超声激活可以将药物靶向肿瘤，增强敏感和MDR肿瘤中药物的细胞毒性，并抑制肿瘤的生长。该项目的具体目的包括：1。扩展一组 /细胞罚款，药物和聚合物胶束，以上技术可能会证明有益，尤其是将紫杉醇纳入药物面板，因为它在常用培养基中的溶解度较低，在多种抗耐药细胞中的活性较低。阿霉素（DOX）和紫杉醇在体外的细胞毒性将在A2780卵巢癌，MCF7乳腺癌和p388白血病细胞系中测量（DWG敏感性和MDR），以及DHD/KLZ/KLZ/TRB Colon Colon Cancer Cancer Cell Line。 2。为了测试以下假设：Micelfar药物递送与超声相结合可抑制体内肿瘤的生长，并增加肿瘤小鼠的存活率。实验将使用皮下生长的药物敏感和MDR A2780和MCF7肿瘤进行，以及在小鼠腹膜腔中生长的p388内部肿瘤；胶束被击倒的DOX和紫杉醇将在有或没有20 kHz超声的情况下交付，以在各种占空比和功率密度的情况下应用于肿瘤。 3。使用DHDMZFRB结肠癌模型扩展体内实验和扩展体内实验。实验将使用胶束封装的DOX与20 kHz和70 kHz超声一起进行。这三个具体目标都集中在临床相关的目标上。