Polymeric nanoparticle as a new platform for high removal of endotoxins from biopharmaceutical solutions
"Presently, approximately one-third of all biopharmaceutical drugs are derived from biological sources like gram-negative bacteria. Gram-negative bacteria like E.coli are much cheaper to cultivate and provide higher biotherapeutic yield compared to mammalian cells. On extracting the useful biotherapeutics from the gram-negative bacterial cells (E.coli), endotoxin present in the bacteria is released in the surrounding media thus contaminating the lifesaving biotherapeutics. Application of the endotoxin-contaminated therapeutics to humans or animals can cause serious health issues like septic shock, tissue injury and ultimately death. Hence, thorough purification of biotherapeutics before parenteral application is necessary. Although there are multiple methods for removing endotoxins, but achieving high protein recovery and purification efficiency are still a challenge. We have demonstrated a cost-effective technology using a biocompatible polymer nanoparticle of approximately 800 nm diameter. The polymeric nanoparticle removed > 99% endotoxins from water, phosphate buffer saline (PBS) and protein solutions including monoclonal antibodies (MAb). It also showed a high protein recovery of ~99 %. Additionally, the polymeric nanoparticle was capable of being reused multiple times after being regenerated. Further, to enhance the throughput, flow properties and to scale up the whole system, the polymeric nanoparticles were incorporated in a portable and flat sheet biofilter. The biofilter is effective in removing > 99% endotoxins from water and protein solutions with a protein recovery of > 90%. Finally, the whole filtration set-up being gravity driven minimized cost"--Abstract, page iv.
Adsorption, Cellulose Acetate (CA) membrane, Endotoxin removal, Lipopolysaccharide (LPS), Polycaprolactone nanoparticles, Protein purification, Chemical Engineering
Missouri University of Science and Technology
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