SBIR Phase II: Manufacturing of Red Blood Cell Membrane-Coated Nanoparticles for detoxification

SBIR 第二阶段：用于解毒的红细胞膜包被纳米颗粒的制造

• 批准号: 1456104
• 负责人: Weiwei Gao
• 金额: $ 75万
• 依托单位: Arytha Biosciences, LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1456104&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Manufacturing; Red

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is enabling the large-scale manufacturing of a red blood cell membrane coated nanoparticle platform, which was previously demonstrated to be capable of absorbing and neutralizing a wide array of hemolytic pathogenic factors, such as bacterial toxins, animal venoms, and auto-reactive immunoglobulin. Comprised entirely of biocompatible and biodegradable materials and coated by cell membranes derived from natural red blood cells, the nanoparticles are able to circulate for an extended period of time in the circulation. Their biomimetic exterior allows them to serve as a decoy to scavenge virulence factors that attack cell membranes. The nanoformulation may be applied against multiple pressing and unmet medical needs, including animal envenoming, autoimmune hemolytic diseases, and bacterial infections. Successful development of the manufacturing process also has broader impact in the field of nanofabrication and nanomedicine development. The proposed project will enable the red blood cell membrane-coated nanoparticles to be manufactured efficiently and reliably at a large scale toward clinical translation. To ensure that the manufactured nanoformulations will have the optimal size, uniformity, biological activity, and performance, advanced fluidics, filtration, microscopy, and particle tracking techniques will be applied for precision nanoparticle preparation and characterization. Specifically, the proposed research activity will focus on the synthesis of uniform polymeric nanoparticles with consistent physicochemical properties, derivation of purified and undisrupted red blood cell membranes, and reliable cell membrane coating over the nanoparticle substrates. The resulting nanoparticles will be thoroughly examined to iteratively improve the preparation process. Optimized manufacturing protocol will be developed for large-scale production of high quality nanoformulations following good manufacturing practices (GMP). The project will facilitate the bench-to-bedside transition of the novel biomimetic nanoparticle platform, which has significant implications in addressing the many major diseases involving protein toxins.

这个小企业创新研究（SBIR）第二阶段项目的更广泛的影响/商业潜力使红细胞膜包被的纳米颗粒平台的大规模制造成为可能，该平台先前被证明能够吸收和中和广泛的溶血性致病因子，如细菌毒素，动物毒液和自身反应性免疫球蛋白。纳米颗粒完全由生物相容性和生物可降解材料组成，并由来自天然红细胞的细胞膜包覆，能够在循环中循环较长时间。它们的仿生外观使它们能够作为诱饵来抑制攻击细胞膜的毒力因子。纳米制剂可以应用于多种紧迫和未满足的医疗需求，包括动物中毒，自身免疫性溶血性疾病和细菌感染。制造工艺的成功开发也对纳米制造和纳米医学开发领域产生了更广泛的影响。拟议的项目将使红细胞膜包覆的纳米颗粒能够有效和可靠地大规模生产，用于临床转化。为了确保制造的纳米制剂将具有最佳的尺寸、均匀性、生物活性和性能，先进的流体学、过滤、显微镜和颗粒跟踪技术将用于精确的纳米颗粒制备和表征。具体而言，拟议的研究活动将集中在合成均匀的聚合物纳米粒子与一致的物理化学性质，纯化和未破坏的红细胞膜的衍生，以及可靠的细胞膜涂层的纳米粒子基板。将对所得纳米颗粒进行彻底检查，以反复改进制备过程。将开发优化的生产方案，以按照良好生产规范（GMP）大规模生产高质量的纳米制剂。该项目将促进新型仿生纳米颗粒平台从实验室到床边的转变，这对解决许多涉及蛋白质毒素的重大疾病具有重要意义。