Precision manufacturing of mucoadhesive nanoparticles using an inkjet- printing platform

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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.