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Extracorporeal Filtration of Thermosensitive Liposomes

热敏脂质体的体外过滤

基本信息

批准号：
10356860
负责人：
Dieter Haemmerich
金额：
$ 17.28万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10356860
关键词：
Biological Blood Blood Circulation Blood Volume Blood flow Cancerous Carotid Arteries Catheters Chest wall structure Clinical Devices Dose Dose-Limiting Doxorubicin Drug Delivery Systems Drug Monitoring Drug Targeting Electromagnetic Fields Encapsulated Excision Filtration Fluorescence Focused Ultrasound Future Goals Heart Heating Hemofiltration High Dose Chemotherapy Hour Hyperthermia In Vitro Knowledge Lasers Light Liposomes Malignant Neoplasms Malignant neoplasm of liver Malignant neoplasm of ovary Maximum Tolerated Dose Mediating Methods Modeling Monitor Organ Patients Pharmaceutical Preparations Phase Phase III Clinical Trials Public Health Rattus Recurrence Rodent Signal Transduction Stream Structure of jugular vein Technology Temperature Testing Therapeutic Time Tissues Toxic effect Translating Treatment Efficacy Tumor Volume base blood filter chemotherapy clinical practice dosage improved in vivo microwave electromagnetic radiation mortality nanoparticle nanoparticle drug novel novel strategies preclinical study prevent prototype scale up side effect targeted delivery tumor ultrasound uptake

项目摘要

PROJECT SUMMARY/ABSTRACT This project will develop a device and perform proof-of-concept studies in a rodent tumor model. The device will remove the chemotherapy agent Doxorubicin from systemic circulation after targeted delivery to tumors. Targeted delivery occurs by temperature sensitive liposomes delivering Doxorubicin to tumor regions. By exposing tumors to hyperthermia (40-42 ºC), drug is locally released and taken up by tumors at high dose. Following hyperthermia, any remaining drug would result in toxicity to non-targeted tissue, and is removed by the proposed extracorporeal filter device with real-time quantification of removed drug amount. If successful, this would represent a novel approach to reduce dose-limiting toxicities, allowing delivery of higher chemotherapy dose and/or reducing toxicity related side effects.

项目总结/摘要该项目将开发一种设备，并在啮齿动物肿瘤模型中进行概念验证研究。该设备将在靶向递送至肿瘤后从体循环中除去化疗剂阿霉素。靶向递送通过将阿霉素递送至肿瘤区域的温度敏感性脂质体发生。通过将肿瘤暴露于高温（40-42 ºC），药物局部释放并以高剂量被肿瘤吸收。在热疗之后，任何剩余的药物将导致对非靶向组织的毒性，并且通过以下方式去除：所提出的体外过滤装置具有去除药物量的实时定量。如果成功，这将代表一种新的方法，以减少剂量限制性毒性，允许提供更高的化疗剂量和/或减少毒性相关的副作用。