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

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.