TEMPERATURE SENSITIVE LIPOSOMES FOR LOCAL DRUG DELIVERY USING MRI AND FU

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 简介： 在过去的十年中，热疗和脂质体药物递送已经被广泛地评价用于药物递送。Needham和合作者[1-2]已经开发了不同的热敏脂质体制剂，其中一种，ThermoDox已被FDA批准用于临床试验。自2003年以来，正在前列腺癌患者中进行的ThermoDox与射频消融治疗相关的试验令人鼓舞。如果分子靶向，则可以改进类似的制剂。磁共振成像与热成像和热疗是改善疾病局部治疗的有力组合。 具体目标： 使用MRI和聚焦超声技术进行的新型分子靶向温度敏感脂质体的合成、表征和癌症疗效研究。 材料和方法： 我们已经开发了一种简单的方法来配制用于癌症治疗的热敏脂质体（TSL）。作为初始模型，生物发光成像用于监测响应于温度升高从TSL中释放的白蛋白。该模型允许一个快速和灵敏的方法优化配方。在优化工艺后，研究了TSL的大小和在缓冲液和血清中的稳定性。使用红细胞测定可能的细胞和膜毒性。还评价了细胞聚集。

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. Introduction: Hyperthermia and the liposomal drug delivery have been extensively evaluated in the past decade for drug delivery. Needham and collaborators [1-2] have developed different thermosensitive liposome formulations of which, one, ThermoDox¿, has been approved by the FDA for use in clinical trials. Since 2003, ongoing trials with ThermoDox in prostate cancer patients in association with radiofrequency ablation therapy have been encouraging. Similar formulations can be improved if molecularly targeted. MR imaging with thermo-mapping, and thermotherapy are powerful combinations for improved local treatment of disease. Specific Aims: Synthesis, characterization, and cancer efficacy studies of new molecularly targeted temperature sensitive liposomes using combined MRI and focused ultrasound techniques. Materials and Methods: We have developed an easy process to formulate thermosensitive liposomes (TSLs) for cancer therapy. As an initial model, bioluminesence imaging was used to monitor the release of luciferin from TSLs in response to increases in temperature. This model allows a quick and sensitive method for optimization of formulations. After optimization of the process, the size and the stability of the TSLs were studied in buffer and serum. Red blood cells were used to determine possible cell and membrane toxicity. Cell aggregation was also evaluated.