Manufacturing Block Copolymer-Based Drug Delivery Vehicles in Microfluidics

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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.