Manufacturing Block Copolymer-Based Drug Delivery Vehicles in Microfluidics

微流控中基于嵌段共聚物的药物输送载体的制造

• 批准号: 447332-2013
• 负责人: Moffitt, Matthew
• 金额: $ 10.16万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Strategic Projects - Group
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=575297
• 关键词: Manufacturing; Block; Copolymer; Based; Drug

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.

将某些治疗剂装载到基于脂质或聚合物的药物递送载体中对于它们的治疗是至关重要的。 成功的管理。药物递送载体通过在长时间内控制释放和优化剂量，或通过靶向需要高剂量的特定组织，来增加水溶性（例如抗癌药物阿霉素）和水不溶性（例如抗癌药物紫杉醇）药物的功效。药物递送系统的关键品质因数是：1）药物载体的形状、尺寸和尺寸均匀性，其对循环时间和生物分布具有强烈影响，以及2）各种药物类型的装载水平和效率。通过与北方脂质公司和Cardiome Pharma公司合作，拟议的工作将开发新的微流体制造平台，用于形成和装载基于嵌段共聚物的药物递送载体。这项工作利用了维多利亚大学和多伦多大学Moffitt-Sinton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域除了形态变化之外还促进颗粒破碎，从而提供了用于控制微流体系统中的自组装的新的“自上而下”手柄。这里要开发的微流体系统将结合这些高剪切力与快速混合和定制的药物注射策略，以实现同时自组装和装载基于嵌段共聚物的药物递送载体。该方法有望提供对形状、尺寸、尺寸均匀性和药物负载的改进控制，从而以较低的成本增加健康益处。本建议涉及“制造业”战略目标领域，特别是研究主题“（a）材料系统”。在该主题中，这项工作侧重于化学（自组装）和微流体（剪切，混合）生产控制的独特交叉点，以实现具有改进功能性能的药物递送纳米材料的新制造工艺。该项目的一项重要产出是为制药、仪器仪表和微系统部门培训高素质人员。