Analytical and Pharmacokinetics Core

分析和药代动力学核心

• 批准号: 8540384
• 负责人: WILLIAM C ZAMBONI
• 金额: $ 7.32万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8540384
• 关键词: Biological Assay; Cancer Center; Carboplatin; Characteristics; Cisplatin; Collaborations; Complex; Coupled; Development; Drug Formulations; Drug Kinetics; Electrospray Ionization; Encapsulated; Evaluation; In Vitro; Instruction; Liposomes; Liquid Chromatography; Mass Spectrum Analysis; Methods; Modeling; Nanotechnology; Parents; Pharmaceutical Preparations; Plasma; Prodrugs; Research Design; Research Methodology; Resolution; Saline; Small Interfering RNA; Sum; Tumor Tissue; design; docetaxel; experience; in vivo; mass spectrometer; nanocarrier; nanoparticle; pre-clinical; tumor

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.

项目摘要（参见说明）： 分析和药代动力学核心 分析和 PK 核心将进行 siRNA、顺铂和帕迪紫杉醇纳米载体制剂的体外和体内 PK 研究。将进行体外研究以评估 siRNA、顺铂和帕紫杉醇纳米颗粒制剂在盐水和血浆中的稳定性和释放特性。体内研究将评估血浆中封装、释放和总（封装+释放）siRNA、顺铂和帕迪他赛的纳米颗粒以及肿瘤和组织中总和的PK处置。血浆中封装和释放的药物的评价将使用SPS进行评价， Zamboni 博士的实验室目前采用电感耦合等离子体质谱 (ICP-MS) 检测血浆、肿瘤和组织中的顺铂和卡铂。他的团队还使用 SPS 方法评估顺铂 (SPI-077) 和 CKD-602 (SCKD602) 聚乙二醇化脂质体制剂的血浆和肿瘤分布。他的团队还评估了肿瘤模型中多西紫杉醇的血浆和肿瘤分布。 Zamboni 博士的实验室对血浆、肿瘤和组织中的多西紫杉醇和帕紫杉醇进行了 LC-MS/MS 检测。正如研究设计和方法部分所述，作为 Zamboni 博士项目 3 的一部分，Zamboni 博士实验室的 SPS 和分析测定将用于评估顺铂和帕迪他赛纳米颗粒制剂的 PK 处置。蒙珀、德西蒙和林。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 纳米载体制剂的开发，作为 Drs. 项目 2 的一部分。黄、金和德西蒙。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。