Characterization of Nanoparticle Batch-To-Batch Variability

Abstract

A central challenge for the safe design of nanomaterials (NMs) is the inherent variability of NM properties, both as produced and as they interact with and evolve in, their surroundings. This has led to uncertainty in the literature regarding whether the biological and toxicological effects reported for NMs are related to specific NM properties themselves, or rather to the presence of impurities or physical effects such as agglomeration of particles. Thus, there is a strong need for systematic evaluation of the synthesis and processing parameters that lead to potential variability of different NM batches and the reproducible production of commonly utilized NMs. The work described here represents over three years of effort across 14 European laboratories to assess the reproducibility of nanoparticle properties produced by the same and modified synthesis routes for four of the OECD priority NMs (silica dioxide, zinc oxide, cerium dioxide and titanium dioxide) as well as amine-modified polystyrene NMs, which are frequently employed as positive controls for nanotoxicity studies. For 46 different batches of the selected NMs, all physicochemical descriptors as prioritized by the OECD have been fully characterized. The study represents the most complete assessment of NMs batch-to-batch variability performed to date and provides numerous important insights into the potential sources of variability of NMs and how these might be reduced.

A Multi-Method Approach for Quantification of Surface Coatings on Commercial Zinc Oxide Nanomaterials

“…A ten-fold higher loading of 454 µmol/g was obtained for USRN-05-NH 2 . The variability in loading level for samples from a single supplier is similar to our previous results for silica nanoparticles [17,19] and literature results for other nanomaterials [18,25,27]. Note that the more than twenty-fold difference in 3-aminopropyl loading for USRN-05-NH 2 and USRN-04-NH 2 cannot be explained by differences in surface area since these samples have nominal diameters of 10-30 and 20 nm, respectively.…”

“…Finally it is useful to compare our data to a recently published study that examined batch-to-batch variability of NP physicochemical properties for silica, cerium dioxide, titanium dioxide and zinc oxide nanoparticles [27]. The materials were all synthesized in-house by the 14 participating laboratories using one or more carefully controlled methods for each material and were characterized for all OECD recommended physicochemical parameters.…”

Zeta‐Potential Read‐Across Model Utilizing Nanodescriptors Extracted via the NanoXtract Image Analysis Tool Available on the Enalos Nanoinformatics Cloud Platform

“…An emerging concept in nanomedicine is the socalled off-target effect, whereby a percentage of the dose never reaches the target site but accumulates elsewhere-detailed descriptors such as the ones described here might also be able, in the future, to provide insights as to which subsets of a NM batch size/shape distribution are likely to have off-target effects, allowing synthesis or separation procedures to remove these "rogue" NMs. These factors could also be utilized in overall NMs production quality control procedures, for analysis of batch-to-batch variability, [38] and potentially to help identify the sources of such variability through analysis of changes in the various ratios as synthesis parameters are varied. [38]…”

Nanomedicines: Challenges and perspectives for future nanotechnology in the healthcare system

“…While scaling up the formulation, the major challenge is to control the growth of the particle. This results in batch to batch variation (Mulhopt and Diabate, 2018).…”