High Throughput Manufacturing of Monodispersed Nanoparticles for Biomedicine

描述（由申请人提供）：第一阶段小型企业技术转移（STTR）项目的重点是开发一种新的平台制造工艺，通过使用大规模纤维流体系统，大规模制备适合生物医学应用的单分散聚合物纳米颗粒（NPs）。尽管通过乳液和纳米沉淀法可重复合成聚合粒子的实验室工艺已经成熟，但在商业化所需的规模上合成这种单分散纳米粒子的合适方法尚未实现。该系统旨在通过提供一种多功能、坚固耐用且易于扩展的工艺来满足这一需求，该工艺可用于在小占地面积内连续制造聚合物NPs。在看到我们的初步数据后，Access制药公司研发高级副总裁David Nowotnik写道：“一种可以在实验室中用于制造医疗应用的单分散纳米颗粒的工艺将是有用的。一个可以很容易地扩展到试点工厂和制造的工厂将对Access和行业非常有用……这个项目对于开发一种新的工业附加值纳米颗粒制造工艺具有巨大的潜力。”第一阶段项目的主要目标是：(1)建立第一阶段纤维流体系统原型，(2)开发利用该原型制备与生物医学应用相关的各种聚合物NP的方法，(3)优化工艺参数以提高吞吐量和对NP大小和单分散性的控制，以及(4)通过确定需要优化的参数，进行彻底的市场分析，并与潜在客户建立合作伙伴关系，为第二阶段做准备。为了实现这些目标，该团队将利用所提出的纤维流体系统，通过纳米沉淀和乳液聚合方法，利用一些单体和聚合物前体，包括丙烯酰胺、n -异丙基丙烯酰胺、聚（乳酸-共乙醇酸）和聚（乳酸）-b-聚（乙二醇），制备疏水、核壳和水凝胶型聚合物NPs。然后，选定数量的配方进行优化，以实现最大的产量，同时保持对NP大小和单分散性的最佳控制。NP配方将通过动态光散射和电子显微镜进行表征。完成第一阶段的目标将展示与批量工艺相比，拟议制造技术在吞吐量和过程控制方面的多功能性和优势，同时指出成功商业化所需的过程优化的主要方面。该项目的成功完成将带来一种低成本、高通量和商业上可行的颗粒制造工艺，可用于生物技术、生物医学研究和制药领域，作为纳米复合材料、涂层、生物分离凝胶中的孔隙素、药物输送系统和造影剂的前体。我们将与Access和其他潜在客户合作，确定将这种制造技术应用于现有和计划中的工厂的最佳方法。

DESCRIPTION (provided by applicant): This Phase I Small Business Technology Transfer (STTR) project focuses on the development of a new platform manufacturing process for large-scale preparation of monodispersed polymeric nanoparticles (NPs) suitable for biomedical applications through the use of a large-scale fiber fluidic system. Although laboratory processes for reproducible synthesis of polymeric particles through emulsion and nanoprecipitation methods have matured, the development of suitable methods for synthesis of such monodispersed NPs in the scales required for commercialization has not been achieved. The proposed system aims to meet this need by providing a versatile, rugged and easily scalable process that can be used for continuous manufacture of polymeric NPs in a small footprint. After seeing our preliminary data, David Nowotnik, Senior Vice President Research and Development at Access Pharmaceuticals wrote: "A process that could be used in the lab to make monodisperse nanoparticles for medical applications would be useful. One that could easily be scaled to pilot plant and manufacturing would be extremely useful to Access and the industry...this project has significant potential for the development of a new value added nanoparticle manufacturing process for industry." The main objectives of the Phase I project will be to: (1) build a Phase I fiber fluidic system prototype, (2) develop methods for the preparation of a variety of polymeric NPs relevant to biomedical applications utilizing this prototype, (3) optimize process parameters to improve throughput and control over NP size and monodispersity, and (4) prepare for Phase II by identifying parameters where optimization will be required, performing thorough market analysis, and establishing partnership with potential customers. To achieve these aims, the team will utilize the proposed fiber fluidic system for the preparation of hydrophobic, core-shell, and hydrogel-type polymeric NPs via nanoprecipitation and emulsion polymerization methods utilizing a number of monomeric and polymeric precursors including acrylamide, N-isopropyl acrylamide, poly(lactic- co-glycolic acid), and poly(lactic acid)-b-poly(ethylene glycol). A select number of formulations will then be optimized to achieve maximal production rates while maintaining optimal control over NP size and monodispersity. NP formulations will be characterized via dynamic light scattering and electron microscopy. Completion of Phase I aims will demonstrate the versatility and benefits of the proposed manufacturing technology in terms of throughput and process control compared to batch processes, while pointing out the main aspects of process optimization required for successful commercialization. Successful completion of this project will result in a low-cost, highly throughput, and commercially viable process for manufacture of particles with applications in biotechnology, biomedical research, and pharmaceutical fields as precursors for nanocomposites, coatings, porogens in biosepartion gels, drug delivery systems, and contrast agents. We will work with Access and other potential customers to identify optimal methods for adoption of this manufacturing technology into existing and planned facilities.