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 Nanoparticles：用于研究粒子效应的"校准质量"纳米工具 治疗药物的生物分布、清除和优化给药属性 纳米颗粒（NP）药物递送系统可以优先递送和释放药物载体中的治疗性货物。 疾病部位的最佳剂量范围，从而有可能改善治疗效果 有效性、减少的副作用和改善的患者依从性。事实上，其中一些改进 已经在第一代纳米技术为基础的治疗，包括Doxil和Abraxane实现。 目前的研究集中在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 在全身给药时将药物递送至疾病部位。的透彻理解 颗粒物理参数的影响：尺寸、形状、表面特性和变形能力; 将有助于合理设计纳米颗粒疗法。非润湿条件下的颗粒复制 模板法是一种新型的纳米尺度的形状特异性粒子的成型方法 由查佩尔山的北卡罗来纳州大学的DeSimone和同事开发。PRINT提供了 这是一个前所未有的机会，可以研究与纳米颗粒输送相关的问题， 重要的是，提供了一个可扩展的文件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 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）， 与药物递送相关的表面（zeta电位、隐形配体）和变形性限制 使用不同的剂型（IV和IP）（目的1）。此外，我们将使用PRINT粒子作为平台来测试 逃避单核吞噬细胞系统（MPS）清除的仿生策略（目的2）。 最后，我们将使用PRINT的多功能性来解决颗粒特征在特定场地中的作用 靶向和控制释放药物在肿瘤床，以提高治疗指数（目标3）。