Precision manufacturing of mucoadhesive nanoparticles using an inkjet- printing platform

控制释放技术使生物活性物质能够在所需的持续时间内可预测地释放到目标环境中并获得最佳的生物反应。我们的实验室专门合成聚合物纳米颗粒以形成纳米级控制释放装置，并研究如何控制这些纳米材料与粘膜结构的相互作用，粘膜结构丰富地存在于覆盖鼻腔、眼部、呼吸道和胃肠道的表面。拟议的NSERC发现赠款旨在建立一个积极的研究计划，以开发能够精确制造用于控制释放应用的粘附性纳米颗粒(MNPs)的新技术。该研究计划将把MNPs的生产从目前的人工连续批量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互关联的纳米颗粒配方参数。利用喷墨打印技术合成纳米粒子的主要优点是它能够以+/-1皮升的分辨率产生大量的纳米粒子。喷墨打印机的产量和分辨率性能对于进行筛选MNPs以获得最佳性能的实验至关重要，而不需要过多的合成时间和试剂。这些创新的变化将使筛选和生产MNPs的制造方法大大提高效率。该计划的短期目标包括：(1)MNP前体的合成，以及研究前体的分子组成对纳米颗粒形成的影响。这项工作将简化制备MNP的步骤，并提高MNP表面粘附性的精确度和控制。(2)使用喷墨打印技术生产MNP。工作重点将集中在调整压电喷墨打印技术以控制MNP的生产过程，并优化MNP前体液滴与水的混合速度，以获得对纳米颗粒形成的精确控制。(3)结合微阵列筛选和喷墨打印技术优化MNP粘附性和药物释放性能。我们将利用喷墨打印机处理少量流体的能力，合成和筛选大量药物包裹纳米粒，以优化MNP的表面和核心特性，用于粘附性和控释应用。从拟议的计划中获得的知识将作为促进我们对聚合物自组装的理解和优化纳米颗粒生产过程的基础。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。这项拟议的研究将创造合成聚合物纳米颗粒的新技术，提供解决方案，以提高制造过程中的精确度和控制，并改进扩大开发，同时将MNP生产中的批次差异降至最低。这项研究计划将导致纳米颗粒形成方面的新发现，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员提供培训，特别是在制药、消费者和纳米设备部门。

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.