Critical aspects in dissolution testing of nanomaterials in the oro-gastrointestinal tract: the relevance of juice composition for hazard identification and grouping

The dissolution of a nanomaterial (NM) in an in vitro simulant of the oro-gastrointestinal (OGI) tract is an important predictor of its biodurability in vivo. The cascade addition of simulated digestive juices (saliva, stomach and intestine), including inorganic/organic biomacromolecules and digestive enzymes (complete composition, referred to as Type 1 formulation), strives for realistic representation of chemical composition of the OGI tract. However, the data robustness requires consideration of analytical feasibility, such as the use of simplified media. Here we present a systematic analysis of the effects exerted by different digestive juice formulations on the dissolution% (or half-life values) of benchmark NMs (e.g., zinc oxide, titanium dioxide, barium sulfate, and silicon dioxide). The digestive juices were progressively simplified by removal of components such as organic molecules, enzymes, and inorganic molecules (Type 2, 3 and 4). The results indicate that the Type 1 formulation augments the dissolution via sequestration of ions by measurable factors compared to formulations without enzymes (i.e., Type 3 and 4). Type 1 formulation is thus regarded as a preferable option for predicting NM biodurability for hazard assessment. However, for grouping purposes, the relative similarity among diverse nanoforms (NFs) of a NM is decisive. Two similarity algorithms were applied, and additional case studies comprising NFs and non NFs of the same substance were included. The results support the grouping decision by simplified formulation (Type 3) as a robust method for screening and grouping purposes. Rational design of analytical criteria to perform dissolution testing of nanomaterials: the relevance of juice composition for hazard identification and grouping.

Automated summary

This article investigates the effects of different digestive juice formulations on the dissolution rate of nanomaterials and evaluates the advantages and disadvantages of different formulations. The results indicate that the Type 1 formulation, which includes enzymes, has a significant impact on the dissolution of nanomaterials and is therefore considered a preferable method for predicting biodurability. Furthermore, the use of simplified formulations for grouping purposes has also been shown to be a robust screening method.