PRINT: Nanoparticles: "Calibration Quality" Nano-tools for Studying the Effect of

打印：纳米颗粒：用于研究效果的“校准质量”纳米工具

• 批准号: 7982949
• 负责人: JOSEPH M. DESIMONE
• 金额: $ 114.88万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7982949
• 关键词: Abraxane; Address; Adverse effects; Beds; Biodistribution; Biological; Biology; Biomimetics; Blood; Blood Circulation; CD 200; CD47 gene; Calibration; Cells; Characteristics; Chemicals; Chemistry; Cisplatin; Complement; Cytotoxin; Disorder by Site; Dosage Forms; Doxorubicin Hydrochloride Liposome; Drug Delivery Systems; Drug usage; Engineering; Epidermal Growth Factor Receptor; Equus caballus; Evaluation; Fungal Proteins; Generations; Goals; Image; In Vitro; Individual; Investigation; Ligands; Measures; Methods; Modeling; Molds; Mononuclear; Mus; Nanotechnology; Normal tissue morphology; North Carolina; Organ; Particle Size; Pharmaceutical Preparations; Printing; Proteins; Research; Role; Shapes; Site; Small Interfering RNA; Solutions; Surface; System; Techniques; Testing; Therapeutic; Therapeutic Index; Time; Tissues; Toxic effect; Transferrin Receptor; Treatment Efficacy; Universities; base; cancer therapy; compliance behavior; controlled release; density; design; dosage; efficacy testing; improved; in vivo; lung xenograft; macrophage; microbial; nanocarrier; nanoparticle; nanoscale; nanotool; next generation; novel; particle; small molecule; therapeutic target; tumor; zeta potential

Project 1: PRINT Nanoparticles: "Calibration Quality" Nano-tools for Studying the Effect of Particle Attributes on Biodistribution, Clearance and Optimized Delivery of Therapeutics Nanoparticle (NP) drug delivery systems can preferentially deliver and release a therapeutic cargo in the optimal dosage range at the site of disease, which in turn has the potential to result in improved therapeutic efficacy, reduced side effects and improved patient compliance. In fact, some of these improvements have already been realized in first generation nanotechnology-based therapeutics, including Doxil and Abraxane. Current research is now focused on engineering the next generation of nanoparticle therapeutics. Challenges in successful design are the numerous biological barriers that impede efficacious and efficient delivery of drugs to the site of the disease upon systemic administration. A thorough understanding of the impact of the physical parameters of the particles¿size, shape, surface characteristics and deformability¿ on biodistribution will aid in the rational design of nanoparticle therapeutics. Particle Replication In Nonwetting Templates is a novel method for the molding of shape-specific particles at the nanometer scale developed by DeSimone and coworkers at the University of North Carolina at Chapel Hill. PRINT offers an unprecedented opportunity to study the problems associated with nanoparticle delivery and, more importanfiy, offers a versafile platform to engineer solutions to these problems. In this project, we will exploit the advantages of PRINT to generate "calibration quality" nano-tools to define the geometric (size, shape), surface (zeta potential, stealthing ligands) and deformability limitations associated with the delivery of drugs using different dosage forms (IV and IP) (Aim 1). In addifion, we will use PRINT particles as a platform to test biomimetic strategies for the evasion of clearance by the mononuclear phagocytic system (MPS) (Aim 2). Finally, we will use the versatility of PRINT to address the role of particle characteristics on site specific targeting and controlled release of drugs in the tumor bed to improve therapeutic index (Aim 3).

项目1：PRINT纳米颗粒：用于研究颗粒效应的“校准质量”纳米工具 治疗药物的生物分布、清除和优化递送的属性 纳米颗粒（NP）药物递送系统可以优先递送和释放治疗药物 疾病部位的最佳剂量范围，进而有可能改善治疗效果 事实上，其中一些改进已经取得了成效、减少了副作用并提高了患者的依从性。 已经在第一代基于纳米技术的疗法中实现，包括 Doxil 和 Abraxane。 目前的研究重点是设计下一代纳米颗粒疗法。 成功设计的挑战是阻碍有效和高效的众多生物屏障 全面了解全身给药后将药物输送到疾病部位。 颗粒物理参数的影响¿尺寸、形状、表面特性和变形能力¿ 生物分布方面的研究将有助于纳米颗粒疗法的合理设计。 模板是一种在纳米尺度上成型特定形状颗粒的新方法 由 DeSimone 和北卡罗来纳大学教堂山分校的同事开发的 PRINT 提供了一种方法。 前所未有的机会来研究与纳米颗粒输送相关的问题，以及更多 importantanfiy，提供了一个 Versafile 平台来设计这些问题的解决方案，在这个项目中，我们将利用它。 PRINT 的优点是生成“校准质量”纳米工具来定义几何形状（尺寸、形状）， 与药物输送相关的表面（zeta 电位、隐形配体）和变形能力 使用不同剂型（IV 和 IP）（目标 1）。此外，我们将使用 PRINT 颗粒作为测试平台。 逃避单核吞噬系统 (MPS) 清除的仿生策略（目标 2）。 最后，我们将利用 PRINT 的多功能性来解决颗粒特征对特定位置的作用 在肿瘤床中靶向和控制释放药物以提高治疗指数（目标 3）。