SummaryDevelopment of reliable cell-based nanotoxicology assays is important for evaluation of potentially hazardous engineered nanomaterials. Challenges to producing a reliable assay protocol include working with nanoparticle dispersions and living cell lines, and the potential for nano-related interference effects. Here we demonstrate the use of a 96-well plate design with several measurement controls and an interlaboratory comparison study involving five laboratories to characterize the robustness of a nanocytotoxicity MTS cell viability assay based on the A549 cell line. The consensus EC 50 values were 22.1 mg/L (95% confidence intervals 16.9 mg/L to 27.2 mg/L) and 52.6 mg/L (44.1 mg/L to 62.6 mg/L) for positively charged polystyrene nanoparticles for the serum-free and serum conditions, respectively, and 49.7 µmol/L (47.5 µmol/L to 51.5 µmol/L) and 77.0 µmol/L (54.3 µmol/L to 99.4 µmol/L) for positive chemical control cadmium sulfate for the serum-free and serum conditions, respectively. Results from the measurement controls can be used to evaluate the sources of variability and their relative magnitudes within and between laboratories. This information revealed steps of the protocol that may need to be modified to improve the overall robustness and precision. The results suggest that protocol details such as cell line ID, media exchange, cell handling, and nanoparticle dispersion are critical to ensure protocol robustness and comparability of nanocytotoxicity assay results. The combination of system control measurements and interlaboratory comparison data yielded insights that would not have been available by either approach by itself.

No abstract

No abstract

Pre-uptake metabolism within the GI tract is responsible for the poor oral bioavailability of numerous drugs. As nanocarriers function as a 'shield', protecting incorporated drugs from enzymatic attack, there is an increasing interest in utilizing them as a tool for overcoming drug degradation. Degradation of carriers resulting in the release of incorporated drugs, mucus permeation, enzyme inhibitory properties and their toxicity are crucial factors that must be taken into account when designing proper nanocarriers. The use of polymer- and lipid-based nanocarriers as protective vehicles are discussed within this review. Lipid-based carriers and novel mucopenetrating particles seem to have a great potential in avoiding metabolizing enzymes. Accordingly, nanocarriers are promising tools for improving the bioavailability of drugs, being sensitive to a pre-uptake metabolism.