Endotoxin hitchhiking on polymer nanoparticles

Abstract

The control of microbial infections is critical for the preparation of biological media including water to prevent lethal septic shock. Sepsis is one of the leading causes of death in the United States. More than half a million patients suffer from sepsis every year. Both gram-positive and gram-negative bacteria are responsible for septic infection by the most common organisms i.e., Escherichia coli and Pseuodomonas aeruginosa. The bacterial cell membrane releases negatively charged endotoxins upon death and enzymatic destruction, which stimulate antigenic response in humans to gram-negative infections. Several methods including distillation, ethylene oxide treatment, filtration and irradiation have been employed to remove endotoxins from contaminated samples, however, the reduction efficiency remains low, and presents a challenge. Polymer nanoparticles can be used to overcome the current inability to effectively sequester endotoxins from water. This process is termed endotoxin hitchhiking. The binding of endotoxin on polymer nanoparticles via electrostatic and hydrophobic interactions offers efficient removal from water. However, the effect of polymer nanoparticles and its surface areas has not been investigated for removal of endotoxins. Poly(ε-caprolactone) (PCL) polymer was tested for its ability to effectively bind and remove endotoxins from water. By employing a simple one-step phase separation technique, we were able to synthesize PCL nanoparticles of 398.3 ± 95.13 nm size and a polydispersity index of 0.2. PCL nanoparticles showed ∼78.8% endotoxin removal efficiency, the equivalent of 3.9 × 10(5) endotoxin units (EU) per ml. This is 8.34-fold more effective than that reported for commercially available membranes. Transmission electron microscopic images confirmed binding of multiple endotoxins to the nanoparticle surface. The concept of using nanoparticles may be applicable not only to eliminate gram-negative bacteria, but also for any gram-positive bacteria, fungi and parasites.

Visible‐Light‐Driven Janus Microvehicles in Biological Media

“…Direct removal of endotoxins from the blood using polymers or magnetic nanocarriers is considered to be an essential tool to improve the patient's health . Polycaprolactone nanoparticles have also been applied for endotoxin removal in water by direct binding …”

“…Such compounds are continuously released at high concentrations in serum and culture media during bacterial growth and proliferation. [24] In ap revious study,o ur group also observed that the micromotors possess am icroporous structure and that endotoxins can penetrate these structures and also interact with the micromotor by adsorption. [22] Most importantly,s epsis is mainly caused by endotoxins through activation of the immune system.…”

PolyBall: A new adsorbent for the efficient removal of endotoxin from biopharmaceuticals

“…PCL NPs were synthesized by the solvent evaporation method which utilized high–speed homogenization and sonication, followed by solvent evaporation, centrifugation to remove surfactants, and then lyophilization 54–58 . A PCL solution at a concentration of 10 mg/ml in ethyl acetate was injected using a syringe pump to a 1% w/v polyvinyl alcohol (PVA) solution prepared with reverse osmosis (RO) water.…”

Subchronic and chronic toxicity evaluation of inorganic nanoparticles for delivery applications

“…Endotoxin contamination can mask the true biological effects of nanoparticles and change the distribution and clearance of nanoparticles in the body. [191][192][193][194][195][196] The acute toxicity due to endotoxin and endotoxin-contaminated nanoparticles is primarily manifested by the cytokine release syndrome. The exaggeration of endotoxin-mediated inflammation by certain nanomaterials is a well-documented problem.…”