Analytical and Pharmacokinetics Core

项目总结（见说明）： 将由分析和PK中心对siRNA、顺铂和紫杉醇的纳米载体制剂进行体外和体内PK研究。将进行体外研究以评估siRNA、顺铂和紫杉醇的纳米颗粒制剂在盐水和血浆中的稳定性和释放特性。体内研究将评估纳米颗粒包封、释放和总和（包封+释放）siRNA、顺铂和紫杉醇在血浆中以及肿瘤和组织中的总和的PK处置。将使用SPS评价血浆中包封和释放的药物， 博士Zamboni的实验室目前有一个电感耦合等离子体质谱法（ICP-MS）测定血浆，肿瘤和组织中的顺铂和卡铂。他的研究小组还使用SPS方法评价顺铂（SPI-077）和CKD-602（SCKD 602）的聚乙二醇化脂质体制剂的血浆和肿瘤处置。他的研究小组还评估了多西他赛在肿瘤模型中的血浆和肿瘤分布。Zamboni博士的实验室有一个LC-MS/MS分析血浆，肿瘤和组织中的多西他赛和帕迪托。如研究设计和方法章节所述，作为Mumper、DeSimone和Lin博士项目3的一部分，将使用Zamboni博士实验室中的SPS和分析测定来评价顺铂和帕迪替尼纳米颗粒制剂的PK分布。我们还计划将我们在设计、执行和分析纳米载体药物与非纳米载体药物临床前PK研究方面的丰富经验应用于siRNA纳米载体制剂的开发，作为Huang、Kim和DeSimone博士项目2的一部分。我们目前正在开发一种使用LTQ-Orbitrap质谱仪通过液相色谱/电喷雾电离高分辨率质谱（LC/ESI-HRMS）检测血浆、肿瘤和组织中siRNA的方法。

PROJECT SUMMARY (See instructions): Analytical and Phartriacokinetics Core In vitro and in vivo PK studies of nanocarrier formulations of siRNA, cisplatin and paditaxel will be performed by the Analytical and PK Core. In vitro studies will be performed to evaluate the stability and released characteristics ofthe nanoparticle formulations of siRNA, cisplatin, and paditaxel in saline and plasma. In vivo studies will evaluate the PK disposition of the nanoparticle encapsulated, released and sum total (encapsulated + released) siRNA, cisplatin, and paditaxel in plasma and sum total in tumor and tissues. The evaluation of encapsulated and released drug in plasma will be evaluated using SPS, Dr. Zamboni's lab currently has an Inductively Coupled Plasma Mass Spectrometry (ICP-MS) assay for cisplatin and carboplatin in plasma, tumor and tissues. His group has also used SPS methods to evaluate the plasma and tumor disposition of pegylated liposomal formulations of cisplatin (SPI-077) and CKD-602 (SCKD602). His group has also evaluated the plasma and tumor disposition of docetaxel in tumor models. Dr. Zamboni's lab has an LC-MS/MS assay for docetaxel and paditaxel in plasma, tumor and tissues. As outlined in the Research Design and Methods section, the SPS and analytical assays in Dr. Zamboni's lab will be used to evaluate the PK disposition of nanoparticle formulations of cisplatin and paditaxel as part of Project 3 by Drs. Mumper, DeSimone and Lin. We also plan on applying our extensive experience in designing, performing, and analyzing preclinical PK studies of nano-carrier agents compared with non-nanocarrier agents to the development of nano-carrier formulations of siRNA as part of Project 2 by Drs. Huang, Kim and DeSimone. We are currently developing an assay for siRNA in plasma, tumor, and tissues via liquid chromatography/electrospray ionization high-resolution mass spectrometry (LC/ESI-HRMS) using an LTQ-Orbitrap Mass Spectrometer.