Acoustically Activated Micellar Drug Delivery

声激活胶束药物输送

基本信息

批准号：
7614401
负责人：
NATALYA Y RAPOPORT
金额：
$ 33.86万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-01-15 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7614401
关键词：
Acoustics Address Adverse effects Animals Blood Circulation Blood capillaries Body Weight Breast Cancer Etiology Cancer Model Cancer Patient Cancerous Cell membrane Cessation of life Clinical Collaborations Combined Modality Therapy Contrast Media Data Diagnostic Dialysis procedure Drug Carriers Drug Delivery Systems Drug Formulations Drug effect disorder Drug-sensitive Elements Emulsions Encapsulated Enhancers Extravasation Flow Cytometry Fluorocarbons Focused Ultrasound Therapy Frequencies Furuncles Future Goals Growth Hour Image In Vitro Individual Injection of therapeutic agent Intravenous Kinetics Malignant neoplasm of ovary Malignant neoplasm of pancreas Measures Mechanics Mediating Medical Micelles Microbubbles Modeling Monitor Multi-Drug Resistance Mus Operative Surgical Procedures Ovarian Carcinoma Particle Size Patients Permeability Pharmaceutical Preparations Phase Physiologic pulse Positioning Attribute Principal Investigator Procedures Property Protocols documentation Publications Quality of life Research Sequoia Shapes Sonication Staging System Techniques Testing Therapeutic Therapeutic Effect Time Transducers Treatment Efficacy Treatment Protocols Treatment Step Treatment outcome Tube Tumor Tissue Tumor Volume Ultrasonic Therapy Ultrasonics Ultrasonography United States Universities Utah Xenograft procedure base capillary cell killing chemotherapy clinical application copolymer density design gemcitabine imaging modality improved in vivo irradiation malignant breast neoplasm nano nanoDroplet nanoparticle neoplastic cell novel novel therapeutics pancreatic neoplasm perfluoropentane pre-clinical preclinical study programs research study sonoporation subcutaneous time use tumor uptake

项目摘要

DESCRIPTION (provided by applicant): The goal of this project is to develop a novel combined ultrasonography/chemotherapy modality for the image-guided targeted tumor therapy using a new class of multifunctional nanoparticles that combine properties of (i) tumor-targeted drug carriers; (ii) ultrasonic drug delivery enhancers; and (iii) ultrasound contrast agents. These formulations comprise mixtures of drug-loaded polymeric micelles and nano- or micro-emulsion droplets stabilized by the same (or different) biodegradable block copolymer. The nanodroplets convert into highly echogenic microbubbles upon systemic injection. The phase state and size of the nanodroplets is controlled by the copolymer/perfluorocarbon concentration ratio and type of the copolymer. Upon injection, the drug-loaded polymeric micelles and nanobubbles extravasate through the defective tumor microvasculature and selectively accumulate in the tumor interstitium. Extravasated nanobubbles aggregate and/or coalesce into highly echogenic microbubbles in the tumor tissue thus serving as potent, tumor-selective, and long-lasting ultrasound contrast agents. These features of the developed systems allow contrast-enhanced diagnostic tumor imaging and tumor chemotherapy being provided by the same "smart" echogenic and targetable polymeric system. Specific Aims include 1. To 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. 2. To test and optimize ultrasound imaging properties of the designed systems using a panel of orthotopically grown internal tumor models. 3. To optimize ultrasound-modulated drug delivery properties of the micelle/microbubble systems in vitro and in vivo using breast cancer and pancreatic cancer tumor models in nu/nu mice. Relevance: The developed systems provide for combining ultrasound tumor imaging and ultrasound-mediated targeted chemotherapy, which is expected to substantially reduce side effects, enhance treatment outcome, and improve quality of life of cancer patients.

描述（由申请人提供）：该项目的目的是使用一种新的多功能纳米颗粒来开发一种新型的超声检查/化学疗法方式，以针对图像引导的靶向肿瘤治疗，以结合（i）肿瘤靶向药物载体的特性；（ii）超声药物递送增强剂；（iii）超声对比剂。这些配方包括由药物加载的聚合物胶束和纳米或微乳液液滴的混合物，该液滴稳定在相同（或不同的）可生物降解的块共聚物中。全身注射后，纳米圆形转化为高度回声的微泡。纳米光的相位状态和大小由共聚物/全氟化合物浓度比和共聚物的类型控制。注射后，载有药物的聚合物胶束和纳米泡会通过有缺陷的肿瘤微脉管系统外出，并选择性地积聚在肿瘤间质中。浸润的纳米泡骨料和/或聚集成肿瘤组织中高度回声的微泡，从而充当有效，肿瘤选择性和持久的超声对比剂。开发系统的这些特征允许对比增强的诊断肿瘤成像和肿瘤化疗由相同的“智能”回声和目标聚合系统提供。具体目的包括1。根据稳定共聚物，气泡大小和治疗性超声参数的类型来测量和优化药物加载微泡的超声反应性（空化特性）。 2。使用原位生长的内部肿瘤模型测试和优化设计系统的超声成像特性。 3。使用乳腺癌和NU/NU小鼠中乳腺癌和胰腺癌肿瘤模型在体外和体内优化胶束/微泡系统的超声调节药物递送特性。相关性：开发的系统提供了将超声肿瘤成像和超声介导的靶向化疗相结合的，预计将大大降低副作用，增强治疗结果并改善癌症患者的生活质量。