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

项目1：印刷纳米颗粒：研究颗粒效应的“校准质量”纳米工具 治疗药物的生物分布、清除和优化给药的属性 纳米粒(NP)给药系统可以优先在体内传递和释放治疗货物 疾病部位的最佳剂量范围，这反过来又有可能导致改善治疗 有效，减少副作用，提高患者的依从性。事实上，这些改进中的一些已经 已经在第一代基于纳米技术的疗法中实现，包括多西他滨和阿布拉克生。 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障碍。 全身给药时将药物输送到疾病部位。透彻了解 物理参数对颗粒大小、形状、表面特性和变形性的影响 关于生物分布的研究将有助于纳米治疗药物的合理设计。非润湿过程中的粒子复制 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。Print提供了一个 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 重要的是，提供了一个非常安全的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 打印的优点是生成“校准质量”的纳米工具来定义几何图形(尺寸、形状)， 与药物输送相关的表面(Zeta电位、隐形配体)和变形能力限制 使用不同的剂型(IV和IP)(目标1)。此外，我们还将使用打印粒子作为测试平台 逃避单核吞噬系统清除的仿生策略(目标2)。 最后，我们将使用印刷的多功能性来解决颗粒特征对站点特定的作用 在肿瘤床内靶向和控制释放药物，以提高治疗指数(目标3)。

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).