LIPOSOMAL DRUG DELIVERY: TUMOR GROWTH DELAY AND DRUG DISTRIBUTION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们已经在动物研究中表明，热疗可以与低温敏感脂质体(LTSL)相结合，以增加对肿瘤的药物输送。LTSL是一种专门的脂质体配方，在温和的高温(42摄氏度)下释放其内容物(阿霉素和锰)，允许总肿瘤药物输送是免费药物的30倍以上。使用核磁共振成像，我们能够在给药过程中和给药后可视化脂质体(由于锰用于脂质体负载)。我们的小组最近发现T1缩短与药物浓度呈线性相关(Ben Viglianti和Mark Dewhirst，与CIVM)。我们假设，药物输送到肿瘤的一个主要障碍是药物输送的宏观变化。以磁共振为工具，通过不同的脂质体和热疗方法来评价药物的浓度和分布。此外，我们建议将药物分布与肿瘤反应相关联。这可能为在临床环境中评估药物输送和预测肿瘤反应提供一种非侵入性的方法。MR研究是上述目标不可或缺的一部分。这种非侵入性成像将能够评估体内的药物传递，并随后与肿瘤反应相关

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have shown in animal studies that hyperthermia can be combined with low temperature sensitive liposomes (LTSL) to increase drug delivery to tumors. The LTSL is a specialized liposome formulation that releases its contents (doxorubicin and manganese) at mildly elevated temperatures (42 C), allowing a total tumor drug delivery of 30 times more than free drug. Using MRI, we are able to visualize the liposomes during and after administration (due to manganese used for liposome loading). Our group has recently shown that T1 shortening is linearly correlated to drug concentration (Ben Viglianti and Mark Dewhirst, with CIVM). We hypothesize that a major barrier for drug delivery to tumors is macroscopic variation in drug delivery. Using MR as a tool, we will evaluate drug concentration and distribution with different methods of liposome and hyperthermia therapy. In addition, we propose to correlate drug distribution with tumor response. This may provide a non-invasive way to evaluate drug delivery and predict tumor response in the clinical setting. The MR studies are integral to the above goals. The non-invasive imaging will allow evaluation of drug delivery in vivo with subsequent correlation to tumor response