Manufacturing Block Copolymer-Based Drug Delivery Vehicles in Microfluidics

将某些治疗药物装载到以脂质或聚合物为基础的药物输送载体中对其 成功的政府。药物输送载体通过长期控制释放和优化剂量，或通过针对需要高剂量的特定组织来提高水溶药物(如抗癌药物阿霉素)和水不溶药物(如抗癌药物紫杉醇)的疗效。药物输送系统的关键优值是：1)药物载体的形状、大小和大小均匀，这对循环时间和生物分布有很大影响；2)不同类型药物的载药量和效率。这项拟议的工作将与Northern Lipids Inc和心脏制药公司合作，开发新的微流控制造平台，用于形成和装载基于嵌段共聚物的药物输送载体。这项工作利用了维多利亚大学和多伦多大学莫菲特-辛顿合作的最新发现。申请人发现，多相反应器内的局部高剪切区除了促进形态变化外，还促进了颗粒的分解，为控制微流控系统中的自组装提供了一种新的“自上而下”的把手。将在这里开发的微流控系统将结合这些高剪切力以及快速混合和量身定制的药物注射策略，以实现嵌段共聚物为基础的药物输送载体的同时自组装和装载。这种方法有望改善对形状、大小、大小一致性和药物载量的控制，从而以更低的成本增加健康效益。该提案涉及“制造”战略目标领域，尤其是“(A)材料系统”这一研究课题。在这一主题中，这项工作侧重于化学(自组装)和微流控(剪切、混合)生产控制的独特交叉，以实现具有改进功能性能的药物输送纳米材料的新制造工艺。该项目的一个重要成果是为制药、仪器仪表和微系统部门培训高素质的人员。

The loading of certain therapeutics into lipid- or polymer-based drug delivery vehicles is critical to their successful administration. Drug delivery vehicles increase efficacy for both water-soluble (e.g. the anticancer drug doxorubicin) and water-insoluble (e.g. the anticancer drug paclitaxel) drugs by controlling release and optimizing dosage over a long period of time, or by targeting specific tissues where high dosages are required. Critical figures of merit for drug delivery systems are: 1) the shape, size, and size uniformity of drug carriers, which have a strong effect on circulation times and bio-distribution, and 2) the loading levels and efficiencies for various drug types. In partnership with Northern Lipids Inc and Cardiome Pharma Corp, the proposed work will develop new microfluidic manufacturing platforms for the formation and loading of block copolymer-based drug delivery vehicles. This work leverages recent findings of the Moffitt-Sinton collaboration at the University of Victoria and the University of Toronto. The applicants discovered that localized high-shear regions within multiphase reactors promote particle break-up in addition to morphology changes, providing a new "top-down" handle for controlling self-assembly in microfluidic systems. The microfluidic systems to be developed here will incorporate these high shear forces in combination with fast mixing and tailored drug injection strategies, to enable simultaneous self-assembly and loading of block copolymer-based drug delivery vehicles. The approach is expected to provide improved control over shape, size, size uniformity, and drug loading, leading to increased health benefits at lower cost. This proposal addresses the "Manufacturing" strategic target area, and most specifically the research topic "(a) Material Systems". Within that topic, this work focuses on a unique intersection of chemical (self-assembly) and microfluidic (shear, mixing) production control, in order to enable new manufacturing processes for drug delivery nanomaterials with improved functional performance. An important output of the project is the training of highly qualified personnel for the pharmaceutical, instrumentation, and microsystems sectors.