In this meta-analysis, we collected 58 publications spanning the last seven decades that reported static in vitro protein gastric digestion results. A number of descriptors of the pepsinolysis process were extracted, including protein type; pepsin activity and concentration; protein concentration; pH; additives; protein form (e.g., ‘native’, ‘emulsion’, ‘gel’, etc.); molecular weight of the protein; treatment; temperature; and half-times (HT) of protein digestion. After careful analysis and the application of statistical techniques and regression models, several general conclusions could be extracted from the data. The protein form to digest the fastest was ‘emulsion’. The rate of pepsinolysis in the emulsion was largely independent of the protein type, whereas the gastric digestion of the native protein in the solution was strongly dependent on the protein type. The pepsinolysis was shown to be strongly dependent on the structural components of the proteins digested—specifically, β-sheet-inhibited and amino acid, leucine, methionine, and proline-promoted digestion. Interestingly, we found that additives included in the digestion mix to alter protein hydrolysis had, in general, a negligible effect in comparison to the clear importance of the protein form or additional treatment. Overall, the findings allowed for the targeted creation of foods for fast or slow protein digestion, depending on the nutritional needs.

Nanoparticles (NPs) are increasingly explored for targeted skin penetration, particularly for pharmaceutical and cosmetic applications. However, the complex system between NP properties, skin structure, and experimental conditions poses significant challenges in predicting their penetration depth and pathways. To what depth do NPs penetrate the skin, and which pathways do they follow? These are the questions which we tried to answer in this paper. A n in‐silico human skin model based on 20 years of literature on NPs skin penetration is developed. The model incorporates 19 independent parameters, including a wide range of NP properties, skin across species, and test conditions. Using random forest analysis coupled with Kennard‐Stone sorting, the model achieves a high predictive accuracy of 95%. The study identifies hair follicle diameter as the most critical factor influencing NP penetration across skin layers, surpassing other skin properties, NP properties, or experimental variables. Pig and rabbit skin are the most suitable models for simulating human skin in NP penetration studies. Additionally, the in‐silico model reveals that NPs in emulsions and oil‐based media predominantly follow the intercellular and transappendageal route. In contrast, those embedded in aqueous media favor the intracellular route. These findings offer insights for optimizing NP‐based drug delivery systems.

Insecticides targeting nicotinic acetylcholine receptors (nAChRs) are used because of their high neuroactive efficacy. However, they can also exert substantial toxic pressure on nontarget aquatic invertebrates. A previous study suggested that irreversible receptor binding is the main driver of thiacloprid bioaccumulation. To determine whether the observed elimination resistance applies to other nAChR-binding insecticides and species, this study investigates five compounds from different substance classes that target nAChRs. Using the two amphipod species, Hyalella azteca and Gammarus pulex, toxicokinetic experiments were combined with assessing receptor binding in vivo and in vitro. The three N-cyanoamidines and N-nitroguanidine neonicotinoids (thiacloprid, acetamiprid, and imidacloprid) and the metabolite imidacloprid-olefin showed resistance toward elimination (i.e., over 15 days of depuration in both amphipod species). This observation could be well described by a two-compartment toxicokinetic (TK)-receptor model (>0.89 R2) with integrated irreversible binding. In contrast, the butenolide flupyradifurone was fully eliminated, and the organic biocide spinosad was eliminated significantly but slowly, both fitted well with a one-compartment TK model (>0.71 R2). These findings demonstrate that receptor-binding specificity and affinity are highly compound class dependent. Although no direct link between receptor binding and acute toxicity could be established, elimination resistance indicates a risk for delayed, sublethal effects that should be critically considered in regulatory risk assessment.