Precision manufacturing of mucoadhesive nanoparticles using an inkjet- printing platform

控制释放技术使得生物活性剂能够可预测地释放到靶向环境中，持续期望的持续时间和最佳的生物反应。我们的实验室专注于合成聚合物纳米颗粒，以制定纳米级控释装置，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覆盖鼻，眼，呼吸道和胃肠道的表面上。 拟议的NSERC发现补助金旨在建立一个积极的研究计划，以开发新技术，使粘膜粘附纳米颗粒（MNP）的精确制造用于控释应用。该研究计划将把MNP的生产从目前的手动连续批量工艺转变为自动喷墨打印平台，该平台将允许精确控制纳米颗粒的形成，以及同时优化多个相互关联的纳米颗粒配方参数。使用喷墨打印技术进行纳米颗粒合成的主要优点是其能够以+/-1皮升分辨率生产大量NP。喷墨打印机的吞吐量和分辨率性能对于进行实验以筛选MNP以获得最佳性能而不需要过多的时间和试剂进行合成至关重要。这些创新性的变化将使筛选和生产MNP的生产方法更加有效。本计画的短期目标包括：（1）合成MNP前驱物，并探讨前驱物分子组成对纳米粒子形成的影响。这项工作将导致简化MNP制备中涉及的步骤数量，并提高MNP表面上的粘膜粘附特性的精度和控制。(2)使用喷墨印刷技术生产MNP。工作将集中在调整压电喷墨打印技术，以控制MNP生产过程，并优化MNP前体液滴与水混合的速率，以便精确控制纳米颗粒的形成。(3)通过结合微阵列筛选和喷墨打印优化MNP粘膜粘附和药物释放特性。我们将利用喷墨打印机的能力，操纵一个小体积的流体，使合成和药物封装的纳米粒子的大型库的筛选，以优化表面和MNP的核心特性，粘膜粘附和控释应用。从拟议的计划中获得的知识将作为推进我们对聚合物自组装的理解和优化纳米颗粒生产工艺的基础。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。 拟议的研究将创造用于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的精度和控制，并改善规模化开发，同时最大限度地减少MNP生产中的批次间差异。这项研究计划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.