Choice of method for endotoxin detection depends on nanoformulation

Nanomedicine (Lond). 2014;9(12):1847-56. doi: 10.2217/nnm.13.157. Epub 2013 Dec 20.

Abstract

Aims: Many nanoparticles interfere with traditional tests to quantify endotoxin. The aim of this study was to compare the performance of limulus amoebocyte lysate (LAL) formats on clinical-grade nanoformulations, to determine whether there were disparate results among formats and to test the applicability of an alternative bioassay (the macrophage activation test [MAT]) for resolving discrepancies, if observed.

Materials & methods: Clinical-grade nanoformulations were tested using turbidimetric, gel-clot and chromogenic LAL. Formulations that cause a discrepancy among LAL tests were also tested by the MAT.

Results & conclusion: The gel-clot LAL method cannot be relied upon to resolve discrepancies among LAL tests for certain nanoformulations. No one LAL format was shown to be optimal for all the tested clinical-grade nanoformulations. The tested alternative bioassay (the MAT) was useful for verifying LAL findings, but only for those nanoformulations not carrying/including cytotoxic drugs.

Keywords: endotoxin; in vitro assay; interference; limulus amoebocyte lysate; lipopolysaccharide nanoparticles; rabbit pyrogen test.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biological Assay / methods*
  • Cell Line
  • Chemistry, Pharmaceutical
  • Endotoxins / analysis*
  • Endotoxins / chemistry
  • Humans
  • Limulus Test / methods
  • Lipopolysaccharides / analysis
  • Lipopolysaccharides / chemistry
  • Macrophage Activation
  • Nanomedicine
  • Nanoparticles / chemistry
  • Pyrogens / analysis

Substances

  • Endotoxins
  • Lipopolysaccharides
  • Pyrogens