Analytical and Pharmacokinetics Core

项目总结(见说明)： 分析和药代动力学核心公司将对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、顺铂和帕迪紫杉醇纳米制剂在生理盐水和血浆中的稳定性和释放特性。体内研究将评估包裹、释放和总计(包裹+释放)siRNA、顺铂和紫杉醇的纳米颗粒在血浆中的PK处置以及总计在肿瘤和组织中的处置。将使用SPS对血浆中的包囊和释放药物进行评价， 赞博尼博士的实验室目前拥有对血浆、肿瘤和组织中顺铂和卡铂的电感耦合等离子体质谱(ICP-MS)分析。他的团队还使用SPS方法评估聚乙二醇化脂质体制剂顺铂(SPI-077)和CKD-602(SCKD602)的血浆和肿瘤处置情况。他的团队还评估了多西他赛在肿瘤模型中的血浆和肿瘤处置情况。赞博尼博士的实验室有一种LC-MS/MS分析方法，可以检测血浆、肿瘤和组织中的多西紫杉醇和帕迪紫杉醇。如研究设计和方法部分所述，作为项目3的一部分，Mumper博士、DeSimone博士和Lin博士将使用赞博尼博士实验室的SPS和分析分析来评估顺铂和紫杉醇纳米制剂的PK处置。我们还计划将我们在设计、执行和分析纳米载体制剂与非纳米载体制剂的临床前PK研究方面的丰富经验应用于siRNA纳米载体配方的开发，这是黄博士、Kim博士和DeSimone博士项目2的一部分。我们目前正在开发一种使用LTQ-Orbitrap质谱仪的高效液相色谱/电喷雾电离高分辨率质谱仪(LC/ESI-HRMS)检测血浆、肿瘤和组织中的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.