High Throughput Manufacturing of Monodispersed Nanoparticles for Biomedicine

用于生物医学的单分散纳米颗粒的高通量制造

• 批准号: 8833373
• 负责人: Tania Betancourt
• 金额: $ 15万
• 依托单位: CHEMTOR, LP
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8833373
• 关键词: Acrylamides; Adoption; Area; Biological Availability; Biomedical Engineering; Biomedical Research; Biosensor; Biotechnology; Businesses; Chemical Engineering; Computer software; Contrast Media; Data; Development; Drug Delivery Systems; Drug Formulations; Electron Microscopy; Emulsions; Engineering; Ethylene Glycols; Evaluation; Fiber; Gel; Glycolates; Human Resources; Hydrogels; Industry; Laboratories; Letters; Marketing; Mediating; Medical; Methods; Modeling; Monitor; Morphology; Nanotechnology; Particle Size; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plants; Polymers; Population; Precipitation; Preparation; Principal Investigator; Process; Production; Reproducibility; Research; Route; Safety; Secure; Small Business Technology Transfer Research; Solid; Suspension substance; Suspensions; System; Technology; Technology Transfer; Tennessee; Testing; Texas; Therapeutic; Thick; Work; Writing; base; bioimaging; clinical practice; commercialization; cost; design; design and construction; ethylene glycol; improved; light scattering; manufacturing process; meetings; method development; nanocomposite; nanometer; nanoparticle; novel; novel diagnostics; operation; particle; photonics; poly-N-isopropylacrylamide; polymerization; process optimization; prototype; public health relevance; research and development; research study; scale up; statistics; success; theranostics

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.

描述（由申请人提供）：该第一阶段小型企业技术转让（STTR）项目的重点是开发一种新的平台制造工艺，通过使用大型纳米粒子来大规模制备适用于生物医学应用的单分散聚合物纳米颗粒（NP）。规模纤维流体系统。尽管通过乳液和纳米沉淀方法可重复合成聚合物颗粒的实验室工艺已经成熟，但尚未开发出商业化所需规模的合成此类单分散纳米颗粒的合适方法。所提出的系统旨在通过提供一种多功能、坚固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纳米粒子。在看到我们的初步数据后，Access Pharmaceuticals 研发高级副总裁 David Nowotnik 写道：“一种可在实验室中用于制造医疗应用单分散纳米颗粒的工艺将非常有用。一种可以轻松扩展到中试工厂的工艺制造对于 Access 和整个行业来说非常有用......该项目对于开发工业用新的增值纳米粒子制造工艺具有巨大的潜力。”第一阶段项目的主要目标是：(1) 构建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纳米颗粒的方法，(3) 优化工艺参数，以提高吞吐量并控制纳米颗粒尺寸和单分散性，(4) 通过确定需要优化的参数、进行彻底的市场分析以及与潜在客户建立合作伙伴关系，为第二阶段做好准备。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，利用多种单体和聚合物前体（包括丙烯酰胺、N-异丙基）制备疏水性、核壳和水凝胶型聚合物纳米粒子丙烯酰胺、聚(乳酸-乙醇酸)和聚(乳酸)-b-聚(乙二醇)。然后将优化选定数量的配方，以实现最大生产率，同时保持对纳米颗粒尺寸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。第一阶段目标的完成将证明所提出的制造技术与批量工艺相比在吞吐量和工艺控制方面的多功能性和优势，同时指出成功商业化所需的工艺优化的主要方面。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，可作为纳米复合材料、涂层、生物分离凝胶中的致孔剂、药物输送系统的前体，应用于生物技术、生物医学研究和制药领域和造影剂。我们将与 Access 和其他潜在客户合作，确定在现有和规划的设施中采用该制造技术的最佳方法。