Continuous-Flow Microfluidic Nanomanufacturing of Nanomedicines

纳米药物的连续流微流控纳米制造

• 批准号: 1562468
• 负责人: Don DeVoe
• 金额: $ 25万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1562468&HistoricalAwards=false
• 关键词: Continuous; Flow; Microfluidic; Nanomanufacturing; Nanomedicines

Nanoparticle-enabled drugs hold enormous potential for improving human health, allowing drug designers to tailor the delivery of therapeutic compounds to specific tissues or cells, and optimize the uptake of drugs into those cells. In particular, the use of lipid vesicles or liposomes as nanoscale drug carriers has resulted in significant advances toward the treatment of a range of cancers. However, the transition of liposomal nanomedicines from the lab to the clinic remains constrained by the lack of nanomanufacturing methods capable of scaling across the full production range. This award will investigate continuous-flow microfluidics technology as a unique scalable approach to bridge this gap. This technology will leverage chemical and physical phenomena across multiple size scales within a continuous-flow microfluidic system, resulting in nanoparticle self-assembly, passive and active drug loading, nanoparticle functionalization, and drug purification and concentration. Individual fluidic modules will be developed and optimized, and sequential modules will be combined in a single continuous-flow nanofactory. The multidisciplinary project will integrate contributions from high school students through graduate researchers, and result in development of a new nanomedicines designed for the treatment of recurrent pediatric neuroblastoma, a high-risk cancer with dismal clinical outcomes.Current techniques for liposomal drug synthesis must be re-engineered at each production scale, introducing manufacturing costs and engineering challenges that present significant barriers to the development of new liposomal drugs. Overcoming this gap is fundamentally a nanomanufacturing challenge. We will develop a multistage microfluidic flow focusing technology as a highly scalable method supporting the full production of liposomal nanomedicines in a continuous-flow process. The studies will yield new insights into the underlying multiscale physics for each processing stage, resulting in improved understanding of the chemophysical processes involved in liposome self-assembly, drug loading, and targeting agent attachment within the microfluidic system. The work will also result in new solutions to the key engineering challenges associated with coupling diverse continuous-flow microfluidic modules for advanced functionalized nanoparticle manufacturing. Performance of the technology will be evaluated using a novel nanomedicine test-bed. Specifically, the award will demonstrate a targeted polypharmaceutical comprising of an amphipathic chemotherapeutic (doxorubicin) together with a lipophilic tyrosine kinase inhibitor (erlotinib) for the treatment of pediatric neuroblastoma. Using this test-bed, a combination of scale-up and scale-out will be explored to provide a unified framework for multi-scale liposomal drug synthesis, vastly increasing the speed and reducing the complexity of nanomedicine manufacturing.

纳米颗粒的药物具有改善人类健康的巨大潜力，使药物设计师可以量身定制治疗化合物向特定的组织或细胞的递送，并优化药物对这些细胞的摄取。特别是，将脂质囊泡或脂质体用作纳米级药物载体已导致对一系列癌症的治疗取得了重大进展。然而，脂质体纳米医学从实验室到诊所的过渡仍然受到缺乏能够在整个生产范围内扩展的纳米制造方法的限制。该奖项将调查连续流微流体技术作为弥合这一差距的独特可扩展方法。这项技术将利用连续流微流体系统中多种大小尺度的化学和物理现象，从而导致纳米颗粒自组装，被动和主动药物加载，纳米颗粒功能化以及药物纯化和浓度。将开发和优化单个流体模块，并将顺序模块组合成单个连续流量纳米效应。多学科项目将通过研究生研究人员通过研究生的贡献，并开发出一种新的纳米药物，旨在治疗复发性的儿科神经母细胞瘤，这是一种高风险的癌症，这是一种高风险的临床效果。具有较低的临床效果。核糖体药物同步的较大范围的制造成本，并引入了质疑，并在制造范围内进行了挑战，并引入了工程，并引入了工程，以使其引入了工程，并构成了工程，并构成了工程的工程。脂质体药物。克服这一差距从根本上是纳米制造挑战。我们将开发一种多阶段的微流体焦点技术作为一种高度可扩展的方法，该方法支持在连续流过程中全面生产脂质体纳米医学。这些研究将为每个处理阶段的基础多尺理物理学提供新的见解，从而提高对脂质体自组装，药物加载和靶向剂的附着在微流体系统中所涉及的化学物理过程的了解。这项工作还将为与高级功能化纳米颗粒制造的各种连续流微流体模块相关的关键工程挑战提供新的解决方案。该技术的性能将使用新型纳米医学测试床进行评估。具体而言，该奖项将展示靶向的多药剂，包括两亲化学治疗疗法（阿霉素）以及亲脂性酪氨酸激酶抑制剂（Erlotinib），用于治疗小学神经细胞瘤。使用此测试床，将探索比例扩大和扩展的组合，为多尺度脂质体药物合成提供一个统一的框架，大大提高了速度并降低了纳米医学制造的复杂性。