Endotoxin contamination in recombinant therapeutics is a widely discussed problem. A recent review highlights similar issues in the field of nanoparticles.
Nanomaterials are commonly contaminated with endotoxin due to their highly reactive surfaces combined with the ability of endotoxin to strongly bind both hydrophobic and positively charged areas. As with recombinant proteins, issues such as therapeutic inactivation, cytokine production, oxidative stress and cytotoxicity have been observed. Detection with LAL is non-optimal, but possible, with the gel clot assay being the most problematic. Serious interference with metal- or silica-containing nanoparticles has been observed. Finally, endotoxin removal is especially difficult with the typical problems encountered using ultrafiltration, size exclusion, two-phase extraction and ion exchange. Even affinity adsorption is problematic since endotoxin tends to bind to strongly to the microparticles. This “endotoxin masking” is a common problem with many therapeutic molecules.