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Fundamental and applied studies in nanoparticle biomedical imaging, stabilization, and processing.

机译：纳米颗粒生物医学成像，稳定化和加工方面的基础研究和应用研究。

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摘要

Nanoparticle carrier systems are gaining importance in the rapidly expanding field of biomedical whole animal imaging where they provide long circulating, real time imaging capability. This thesis presents a new paradigm in imaging whereby long wavelength fluorescent or photoacoustically active contrast agents are embedded in the hydrophobic core of nanocarriers formed by Flash NanoPrecipitation. The long wavelength allows for improved optical penetration depth. Compared to traditional contrast agents where fluorophores are placed on the surface, this allows for improved signal, increased stability, and molecular targeting capabilities. Several types of long wavelength hydrophobic dyes based on acene, cyanine, and bacteriochlorin scaffolds are utilized and animal results obtained for nanocarrier systems used in both fluorescent and photoacoustic imaging modes. Photoacoustic imaging is particularly promising due to its high resolution, excellent penetration depth, and ability to provide real-time functional information.;Fundamental studies in nanoparticle stabilization are also presented for two systems: model alumina nanoparticles and charge stabilized polystyrene nanoparticles. Motivated by the need for stable suspensions of alumina-based nanocrystals for security printing applications, results are presented for the adsorption of various small molecule charged hydrophobes onto the surface of alumina nanoparticles. Results are also presented for the production of charge stabilized polystyrene nanoparticles via Flash NanoPrecipitation, allowing for the independent control of polymer molecular weight and nanoparticle size, which is not possible by traditional emulsion polymerization routes.;Lastly, methods for processing nanoparticle systems are explored. The increasing use of nanoparticle therapeutics in the pharmaceutical industry has necessitated the development of scalable, industrially relevant processing methods. Ultrafiltration is particularly well suited for concentrating and purifying macromolecular suspensions. Processing parameters are defined and optimized for PEGylated nanoparticles, charge stabilized latices, and solutions of albumin. The fouling characteristics are compared and scale-up recommendations made. Finally, a pilot scale spray drying system to produce stable nanocrystalline powders of highly crystalline drugs which cannot be stably formulated by traditional spray drying methods is presented. To accomplish this, a novel mixing device was developed and implemented at pilot scale, demonstrating feasibility beyond the lab scale.
机译：纳米颗粒载体系统在迅速发展的生物医学全动物成像领域中正变得越来越重要，在该领域中，纳米颗粒载体系统提供了长期的循环实时成像能力。本论文提出了一种新的成像方法，将长波长荧光或光声活性造影剂嵌入由Flash NanoPrecipitation形成的纳米载体的疏水核中。长波长可以改善光学穿透深度。与将荧光团放置在表面上的传统造影剂相比，这可以改善信号，提高稳定性和分子靶向能力。利用了基于并苯，花青和细菌绿素支架的几种类型的长波长疏水染料，并获得了用于荧光和光声成像模式的纳米载体系统的动物结果。光声成像由于其高分辨率，出色的穿透深度和提供实时功能信息的能力而特别有前途。纳米颗粒稳定化的基础研究还针对两种系统进行了研究：模型氧化铝纳米颗粒和电荷稳定的聚苯乙烯纳米颗粒。出于对用于安全印刷应用的基于氧化铝的纳米晶体的稳定悬浮液的需求的推动，提出了将各种小分子带电荷的疏水物吸附到氧化铝纳米颗粒表面上的结果。还给出了通过Flash NanoPrecipitation生产电荷稳定的聚苯乙烯纳米颗粒的结果，从而可以独立控制聚合物的分子量和纳米颗粒的大小，这是传统乳液聚合路线无法实现的。最后，探索了处理纳米颗粒系统的方法。纳米颗粒疗法在制药工业中的越来越多的使用已需要开发可扩展的，与工业相关的加工方法。超滤特别适合于浓缩和纯化大分子悬浮液。定义并优化了工艺参数，以用于PEG化的纳米颗粒，电荷稳定的胶乳和白蛋白溶液。比较结垢特性并提出放大建议。最后，提出了一种中试规模的喷雾干燥系统，用于生产稳定的高结晶性药物纳米晶体粉末，而传统的喷雾干燥方法无法稳定地配制这些粉末。为此，开发了一种新型的混合装置，并在中试规模下实施，证明了超出实验室规模的可行性。

著录项

  • 作者

    Pansare, Vikram J.;

  • 作者单位

    Princeton University.;

  • 授予单位 Princeton University.;
  • 学科 Nanoscience.;Chemical engineering.;Materials science.
  • 学位 Ph.D.
  • 年度 2015
  • 页码 466 p.
  • 总页数 466
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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