Precision manufacturing of mucoadhesive nanoparticles using an inkjet- printing platform

控制释放技术使生物活性药物能够在预期的时间内释放到目标环境中，并产生最佳的生物反应。我们的实验室专注于合成聚合物纳米颗粒以制备纳米级控释装置，并研究如何控制这些纳米材料与粘膜结构的相互作用，这些结构大量存在于鼻腔，眼部，呼吸道和胃肠道的表面。拟议的NSERC发现基金旨在建立一个积极的研究计划，以开发用于控制释放应用的黏附纳米颗粒（MNPs）精密制造的新技术。该研究项目将把纳米颗粒的生产从目前的手工批量生产工艺转变为自动化喷墨打印平台，该平台将允许精确控制纳米颗粒的形成，以及同时优化多个和相关纳米颗粒配方参数。使用喷墨打印技术合成纳米颗粒的主要优点是它能够以+/- 1皮升的分辨率生产大量纳米颗粒。喷墨打印机的吞吐量和分辨率性能对于进行实验筛选MNPs以获得最佳性能而不需要过多的时间和合成试剂至关重要。这些创新的变化将使筛选和生产MNPs的制造方法更加有效。拟建项目的短期目标包括：(1)合成MNP前体，并研究前体分子组成对纳米颗粒形成的影响。这项工作将简化MNP制备的步骤，提高MNP表面粘接性能的精度和控制。(2)采用喷墨打印技术生产MNP。工作重点是调整压电喷墨打印技术来控制MNP的生产过程，并优化MNP前驱体液滴与水的混合速率，以精确控制纳米颗粒的形成。(3)结合微阵列筛选和喷墨打印优化MNP黏附和释药性能。我们将利用喷墨打印机操纵小体积流体的能力来合成和筛选大量药物封装纳米颗粒库，以优化MNP的表面和核心性能，以实现黏附和控释应用。从该计划中获得的知识将作为推进我们对聚合物自组装和优化纳米颗粒生产工艺的理解的基础。它还将为筛选和生产纳米颗粒的更有效的制造方法提供基础。拟议的研究将创造合成聚合物纳米颗粒的新技术，为提高制造过程的精度和控制提供解决方案，并在最大限度地减少MNP生产中批次之间的差异的同时，改善规模化开发。这一研究项目将导致纳米颗粒形成的新发现，并将有助于保持加拿大先进材料制造业在全球经济中的竞争优势。这项研究还将为先进制造业的高素质人才提供培训，特别是在制药、消费者和纳米器件领域。

Controlled release technologies have enabled the predicable release of bioactive agents to a targeted environment for a desired duration and optimal biological responses. Our laboratory specializes in synthesizing polymeric nanoparticles to formulate nano-scaled controlled release devices, and in studying how to control the interactions of these nanomaterials with mucosal structures, which are abundantly present on the surfaces covering the nasal, ocular, respiratory, and gastrointestinal tracts. The proposed NSERC Discovery Grant aims to establish an active research program to develop new technologies that enable the precision manufacturing of mucoadhesive nanoparticles (MNPs) for controlled release applications. The research program will transform the production of MNPs from the current manual serial bulk processes to an automated inkjet-printing platform that will allow precise control of nanoparticle formation, as well as, concurrent optimization of multiple and interrelated nanoparticle formulation parameters. The main advantage of using inkjet-printing technologies for nanoparticle synthesis is its capability of producing a large quantity of NPs at +/- 1 picoliter resolution. The throughput and resolution performance of the inkjet printer is essential for conducting experiments to screen MNPs for optimal properties without requiring excessive time and reagents for synthesis. These innovative changes will enable a substantially more efficient manufacturing approach for screening and producing MNPs. The short-term objectives of the proposed program include: (1) Synthesis of MNP precursors, and an investigation of the effect of precursors’ molecular compositions on nanoparticle formation. The work will lead to simplifying the number of steps involved in the preparation of MNP, and to improving the precision and control of mucoadhesive properties on the surface of MNP. (2) Production of MNP using Ink-jet printing technology. Work will focus on tuning the piezoelectric inkjet printing technology to control the MNP production process, and to optimize the rate of the MNP precursor droplet mixing with water, in order to gain precise control of the nanoparticle formation. (3) Optimization of MNP mucoadhesion and drug release properties by combining microarray screening and inkjet printing. We will utilize the inkjet printer’s capability of manipulating a small volume of fluids to enable the synthesis and the screening of a large library of drug encapsulated nanoparticles in order to optimize the surface and the core properties of MNP for mucoadhesion and controlled release applications. Knowledge obtained from the proposed program will serve as the foundation for advancing our understanding on polymer self-assembly and for optimizing nanoparticle production processes. It will also provide the foundation for a substantially more efficient manufacturing approach for screening and producing nanoparticles. The proposed research will create new technologies for synthesizing polymeric nanoparticles, provide solutions to enhance precision and control in the manufacturing process, and improve scale-up development while minimizing batch-to-batch variations in MNP production. This research program will lead to new discoveries on nanoparticle formation and it will help maintain the competitive advantage of the Canadian advanced materials manufacturing industries in the global economy. This research will also provide training for highly qualified personnel in the advanced manufacturing industry, particularly in the pharmaceuticals, consumers and nanodevices sectors.