Acoustically Activated Micellar Drug Delivery

声激活胶束药物输送

• 批准号: 7418049
• 负责人: NATALYA Y RAPOPORT
• 金额: $ 35.1万
• 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 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7418049
• 关键词: Acoustics; Address; Adverse effects; Animals; Biodistribution; Blood Circulation; Blood capillaries; Blood flow; Cancer Patient; Cell membrane; Cells; Class; Clinical; Condition; Contrast Media; Data; Development; Diagnostic; Dialysis procedure; Doxorubicin; Drug Carriers; Drug Delivery Systems; Elasticity; Elements; Emulsions; Encapsulated; Endothelial Cells; Endothelium; Enhancers; Extravasation; Flow Cytometry; Fluorocarbons; Focused Ultrasound Therapy; Frequencies; Furuncles; Future; Goals; Greater sac of peritoneum; Heating; Hour; Housing; Image; In Situ; In Vitro; Individual; Injection of therapeutic agent; Label; Life; Localized; Magnetic Resonance Imaging; Measures; Mediation; Medical; Micelles; Microbubbles; Micrometastasis; Modality; Modeling; Monitor; Mus; Normal tissue morphology; Numbers; Ovarian Carcinoma; Particle Size; Permeability; Pharmaceutical Preparations; Phase; Physical Dialysis; Physiologic pulse; Physiological; Positioning Attribute; Positron-Emission Tomography; Primary Neoplasm; Procedures; Property; Protein Overexpression; Protocols documentation; Publications; Pulse taking; Purpose; Quality of life; Range; Rate; Sequoia; Shapes; Site; Sonication; Staging; Sterilization for infection control; Surface; System; Techniques; Temperature; Testing; Therapeutic; Time; Transducers; Treatment Cost; Treatment Protocols; Treatment Step; Treatment outcome; Tube; Tumor Tissue; Tumor Volume; Tumor-Associated Vasculature; Ultrasonic Therapy; Ultrasonics; Ultrasonography; Vascular Endothelial Growth Factor Receptor; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors; base; capillary; caprolactone; chemotherapy; copolymer; density; design; in vivo; instrument; intravenous injection; malignant breast neoplasm; monolayer; nano; nanoDroplet; nanoemulsion; nanoforms; nanoscale; neoplastic cell; neovascular; novel; particle; perfluoropentane; research study; size; subcutaneous; submicron; tumor; tumor growth; uptake; venule

The goal of this project is to develop a novel chemotherapeutic modality for the ultrasound image-guided targeted tumor therapy. This is realized by developing a new class of agents that combine the properties of a drug carrier and ultrasound contrast agent in a nano- or micro-particle system. The system comprises a mixture of drug-loaded polymeric micelles and nano- or micro-emulsion droplets stabilized by the same or different biodegradable block copolymer. The nano- or micro-emilsion droplets convert into microbubbles in situ upon heating to physiological temperatures. Upon injection, the drug-loaded polymeric micelles cross the tumor vasculature and accumulate in the tumor interstitium while the microbubbles remain in circulation and can be molecularly targeted to a neovascular endothelium of primary tumors and micrometastases. The designed systems are highly echogenic, which allows contrast-enhanced diagnostic tumor imaging prior to therapy. Following tumor imaging, therapeutic ultrasound is directed to tumor to effectively release drug from the micelles and nano/microbubbles and enhance intracellular drug uptake. The designed microbubbles combine four important functions: (i) drug carriers; (ii) enhancers of drug release from the carrier; enhancers of intracellular drug uptake by tumor cells; and (iii) ultrasound contrast agents. Specific Aims include: 1. Characterize novel imaging/delivery systems with respect to phase state, particle size, drug loading and release. 2. Measure and optimize ultrasound responsiveness (cavitation properties) of drug-loaded microbubbles depending on the type of the stabilizing copolymer, bubble size, and therapeutic ultrasound parameters. 3. Optimize ultrasound parameters and drug delivery properties of the micelle/microparticle systems using breast cancer tumor model. 4. Test and optimize ultrasound imaging properties of the designed systems. 5. Synthesize molecularly targeted nano/microparticle systems by conjugating VEGF to a bubble-stabilizing copolymer. Measure microbubble retention by neovasculature endothelial cells. Relevance: The development of dual-modality imaging/chemotherapy drug delivery systems for use with dual-modality imaging/treatment ultrasound instruments is very timely. The proposed imaging/treatment modality avoids limitations associated with current ultrasonic ablative therapies and is expected to reduce side effects of chemotherapy and enhance treatment outcome and quality of life of cancer patients.

该项目的目的是为超声图像引导开发一种新型的化学治疗方式 靶向肿瘤疗法。这是通过开发新的代理类别来实现的，该类别结合了 纳米或微颗粒系统中的药物载体和超声对比剂。该系统包括 由同一或相同或 不同的可生物降解块共聚物。纳米或微emilsion液滴转换为微泡中的微泡 供暖到生理温度时。注射后，载有药物的聚合物胶束越过 肿瘤脉管系统并积聚在肿瘤间质中，而微泡则保持循环和 可以将分子靶向原发性肿瘤和微量转移的新生血管内皮。这 设计的系统具有高度回声，它允许对比增强的诊断肿瘤成像 治疗。肿瘤成像后，将治疗性超声引向肿瘤，以有效地释放药物 胶束和纳米/微泡并增强细胞内药物的摄取。设计的微泡 结合四个重要功能：（i）药物载体； （ii）从载体中释放药物的增强子；增强剂 肿瘤细胞的细胞内药物摄取； （iii）超声对比剂。具体目的包括：1。 相对于相位状态，粒径，药物载荷和 发布。 2。测量并优化了载有药物的超声反应性（空化特性） 微泡取决于稳定共聚物，气泡尺寸和治疗性超声 参数。 3。优化胶束/微粒的超声参数和药物输送特性 使用乳腺癌肿瘤模型的系统。 4。测试和优化的超声成像特性 设计系统。 5。通过将VEGF结合到A 气泡稳定的共聚物。测量神经内皮细胞的微泡保留。 相关性：双模式成像/化学疗法药物输送系统的开发 双模式成像/处理超声仪器非常及时。提出的成像/处理 模态避免了与当前超声消融疗法相关的局限性，并有望减少 化学疗法的副作用并增强癌症患者的治疗结果和生活质量。