Biocompatible γ-cyclodextrin metal-organic frameworks (γ-CD-MOFs) have been reported to improve the apparent solubility and bioavailability of encapsulated bioactive compounds, including curcumin, potentially enabling sustained delivery. However, disintegration of γ-CD-MOFs may "release" encapsulated curcumin within the cavity in its insoluble crystallized form. This study evaluated whether the presence of micelles (at a concentration above curcumin's maximum solubility) would be able to take up the "released" curcumin from γ-CD-MOFs to further increase its apparent solubility. Release in the presence of a micellar phase was compared to curcumin encapsulated within γ-CD-MOFs alone. Results demonstrated that Tween 80 solubilized higher curcumin concentrations compared to oleic acid and bile salts. Dispersed in combination with Cur- γ-CD-MOFs, it was found that Tween 80 and oleic acid can improve the apparent solubility of curcumin, 5× and 1.5× higher than in the absence of micelles of these surfactants, respectively, whereas bovine bile salts exhibited a negative effect, due to a displacement of curcumin from within cavity of γ-CD-MOFs. Moreover, it was also found that Tween 80 was less affected by pH and salt concentrations due to its nonionic nature. In vitro digestion (via the INFOGEST protocol) revealed an 8-fold increase in apparent solubility of curcumin with bile salts and a 53-fold increase when combining bile salts and γ-CD-MOFs, achieving bioaccessibility of 2 % and 16 %, respectively. In conclusion, this research revealed the evaluation of γ-CD-MOFs' functionality for delivery and controlled release, with the possibility of an emulsion system boosting the fraction of curcumin that would potentially be bioavailable.

2AbstractBackgroundGastric fluid plays a key role in food digestion and drug dissolution, therefore, the amount of gastric fluid present in a fasted state may influence subsequent digestion and drug delivery. We aimed to describe intra- and interindividual variation in fasted gastric content volume (FGCV) and to determine the association with age, sex, and body size characteristics.MethodsData from 24 MRI studies measuring FGCV in healthy, mostly young individuals after an overnight fast were pooled. Analysis included 366 participants with a total of 870 measurements. Linear mixed model analysis was performed to calculate intra- and interindividual variability and to assess the effects of age, sex, weight, height, weight*height as a proxy for body size, and body mass index (BMI).ResultsFGCV ranged from 0 to 156 mL, with a mean (± SD) value of 33 ± 25 mL. The overall coefficient of variation within the study population was 75.6%, interindividual SD was 15 mL, and the intraindividual SD was 19 mL. Age, weight, height, weight*height, and BMI had no effect on FGCV. Women had lower volumes compared to men (MD: -6 mL), when corrected for the aforementioned factors.ConclusionFGCV is highly variable, with higher intraindividual compared to interindividual variability, indicating that FGCV is subject to day-to-day and within-day variation and is not a stable personal characteristic. This highlights the importance of considering FGCV when studying digestion and drug dissolution. Exact implications remain to be studied.GRAPHICAL ABSTRACTKEY POINTSFasted gastric content volume is highly variable, both within an individual and between individuals, and should range between 0 and 138 mL in healthy young individuals.Women have lower fasted gastric content volume compared to men; age, body weight and body size were not associated with differences in fasted gastric content volume.Fasted gastric content volume can impact both digestion and drug dissolution, although exact implications of the observed variations remain to be studied.

To get the most accurate food digestion-related data, and how this affects nutrient absorption, it is critical carefully simulate human digestion systems using model settings. In this study, the uptake and transepithelial transportation of dietary carotenoids was compared using two different models that have previously been used assess nutrient availability. The permeability of differentiated Caco-2 cells and murine intestinal tissue were tested using all-trans-beta-carotene and lutein prepared in artificial mixed micelles and micellar fraction from orange-fleshed sweet potato (OFSP) gastrointestinal digestion. Transepithelial transport and absorption effi-ciency were then determined using liquid chromatography tandem-mass spectrometry (LCMS-MS). Results showed that the mean uptake for all-trans-beta-carotene in the mouse mucosal tissue was 60.2 +/- 3.2% compared 36.7 +/- 2.6% in the Caco-2 cells with the mixed micelles as the test sample. Similarly, the mean uptake was higher in OFSP with 49.4 +/- 4.1% following mouse tissue uptake compared to 28.9 +/- 4.3% using Caco-2 cells for the same concentration. In relation to the uptake efficiency, the mean percentage uptake for all-trans-beta-carotene from artificial mixed micelles was 1.8-fold greater in mouse tissue compared to Caco-2 cells (35.4 +/- 1.8% against 19.9 +/- 2.6%). Carotenoid uptake reached saturation at 5 mu M when assessed with the mouse intestinal cells. These results demonstrate the practicality of employing physiologically relevant models simulating human intestinal absorption processes that compares well with published human in vivo data. When used in combination with the Infogest digestion model, the Ussing chamber model, using murine intestinal tissue, may thus be an efficient predictor of carotenoid bioavailability in simulating human postprandial absorption ex vivo.

The rapidly ageing population requires food products that meet their specific physiological needs and have pleasurable sensory characteristics. Conventionally, rheology is used as a food formulation design tool that allows food bolus to be swallowed safely. Nevertheless, in the last few decades, there has been increased understanding of soft tribology of thickeners and fabrication of biologically relevant tribological set-ups. We discuss how this knowledge can offer a solid baseline to employ tribology as a design tool to tailor foods for the elderly population with various oral insufficiencies. In-depth characterisation of oral conditions of the elderly population is a necessary undertaking to fabricate tribology apparatus that better emulates in vivo conditions, to allow rational design of food products for this growing population.

Food industries are challenged to reformulate foods and beverages with higher protein contents to lower fat and sugar content. However, increasing protein concentration can reduce sensory acceptability due to astringency perception. Since the properties of food-saliva mixtures govern mouthfeel perception, understanding how saliva and protein interact is key to guide development of future protein-rich reformulations with optimal sensory attributes. Hence, this systematic review investigated protein-saliva interaction using both model and real human saliva, including a quality assessment. A literature search of five databases (Medline, Pubmed, Embase, Scopus and Web of Science) was undertaken covering the last 20 years, yielding 36 604 articles. Using pre-defined criteria, this was reduced to a set of 33 articles with bulk protein solutions (n = 17), protein-stabilized emulsions (n = 13) and protein-rich food systems (n = 4). Interaction of dairy proteins, lysozyme and gelatine with model or human saliva dominated the literature. The pH was shown to have a strong effect on electrostatic interaction of proteins with negatively-charged salivary mucins, with greater interactions occurring below the isoelectric point of proteins. The effect of protein concentration was unclear due to the limited range of concentrations being studied. Most studies employed a 1 : 1 w/w protein : saliva ratio, which is not representative of true oral conditions. The interaction between protein and saliva appears to affect mouthfeel through aggregation and increased friction. The searches identified a gap in research on plant proteins. Accurate simulation of in vivo oral conditions should clarify understanding of protein-saliva interaction and its influence on sensory perception.

Although oral drug delivery is the preferred administration route and has been used for centuries, modern drug discovery and development pipelines challenge conventional formulation approaches and highlight the insufficient mechanistic understanding of processes critical to oral drug absorption. This review presents the opinion of UNGAP scientists on four key themes across the oral absorption landscape: (1) specific patient populations, (2) regional differences in the gastrointestinal tract, (3) advanced formulations and (4) food-drug interactions. The differences of oral absorption in pediatric and geriatric populations, the specific issues in colonic absorption, the formulation approaches for poorly water-soluble (small molecules) and poorly permeable (peptides, RNA etc.) drugs, as well as the vast realm of food effects, are some of the topics discussed in detail. The identified controversies and gaps in the current understanding of gastrointestinal absorption-related processes are used to create a roadmap for the future of oral drug absorption research.

Emerging antibiotic resistance in pathogens has posed considerable challenges to explore and examine the natural antimicrobials (NAMs). Due to the labile nature of NAMs, nano-delivery systems (NDS) are required to protect them from physiological degradation and allow controlled delivery to the targeted site of infection. In this study, corona modified NDS were developed using bovine serum albumin (BSA) on a chitosan core (CS) for sustained delivery of carvacrol (CAR), a natural antimicrobial agent, in the intestine. The optimal nanoformulations of the core (CS-NDS) and corona modified (BSA-CS-NDS) systems were fabricated with an average diameter of 52.4 +/- 10.4 nm and 202.6 +/- 6 nm, respectively. A shift in zeta-potential (ZP) from positive (+21 +/- 3.6 mV) to negative values (-18 +/- 2.6 mV) confirmed the electrostatic deposition of BSA corona on CS core. Under the influence of various simulated gastrointestinal conditions, BSA corona provided extra stability to NDS (ZP -38.5 mV), by ensuring delayed release and limited degradation in the gastric conditions. Mucoadhesive studies with quartz crystal microbalance with dissipation (QCM-D) revealed that BSA corona reduced the mucoadhesion of NDS at gastric pH, which enabled the effective delivery of CAR to the intestinal phase for successful eradication of Salmonella enterica. (C) 2020 Elsevier B.V. All rights reserved.

Horse milk is a valuable raw material and a very attractive alternative for scientific research to address the issue of cow milk (CM) allergy due to its protein profile. A decrease in immunoreactive properties can be achieved by thermal, enzymatic, and hydrolytic processing. Therefore, the aim of this study was to explore the possibility of reducing the immunoreactivity of horse milk proteins by microbial transglutaminase (TG) polymerization. To determine how TG linking alters immunoreactivity under simulated digestion of the examined milk, analyses were performed before, during, and after digestion. The dose-dependent (1, 10, and 100 U) effects of microbial TG on horse and cow milk were analyzed. A consecutive 3-stage digestion was simulated with salivary, gastric, and intestinal fluids. The effects of digestion were analyzed by SDS-PAGE, particle size analysis, and size-exclusion chromatography. Immunoreactivity was assessed using competitive ELISA (β-lactoglobulin and α-casein) and immunodot (sera from 7 patients aged 3 to 13 years who are allergic to CM proteins). Horse milk contained almost half of the amount of total proteins in CM. The dose 1 U/g of total milk protein changed the immunoreactivity of both cow and horse milk. With increasing TG doses, α-casein immunoreactivity increased, and β-lactoglobulin decreased. After total digestion, horse milk was characterized by 2.4-fold lower average IgE and 4.8-fold lower IgG reactivity than CM. We found that TG alters the IgE and IgG reactivity of CM after in vitro digestion. Horse milk was less reactive to IgE and IgG than was CM, with animal and patient sera. The effect of TG on immunoreactivity depends on enzyme quantity and milk protein type. The diet based on modified horse milk proteins could be an alternative for some patients with CM protein allergy; however, confirmation through clinical trials is needed.

Unravelling the fate of food in the gastrointestinal tract is essential to better understand the health effects of the food and to fight against diet-related pathologies such as cardiovascular diseases and type-2 diabetes. Digestion is the process that transforms food into nutrients. The first step of digestion occurs in the mouth, where mastication transforms solid and semi-solid foods into particles while mixing with saliva allows bolus formation and initiates digestion of carbohydrates.Then the bolus is transferred into the stomach, where acid conditions and specific enzymes (pepsin, gastric lipase) start hydrolyzing macronutrients like proteins and triglycerides. The next step occurs in the small intestine, where other digestive enzymes further degrade macronutrients allowing their absorption. In the small intestine, proteins are hydrolyzed by trypsin, chymotrypsin, elastase, carboxypeptidase etc, lipids by pancreatic lipases, and carbohydrates by pancreatic amylase. Small intestinal digestion is completed by the enzymes of the brush border membrane that release macronutrients, which can be absorbed by enterocytes to reach the bloodstream. Undigested material, fiber for example, reaches the large intestine where it is further metabolized by the intestinal microbiota. Investigating food digestion requires the use of models and a myriad of in vitro (static and dynamic), animal and human models have been described in the literature with the objectives of understanding the fate of food in the gastrointestinal tract. In particular, static in vitro digestion simulations are extremely popular because they are very easy to use and do not require sophisticated equipment. They have been shown to be adapted for screening large series of similar samples in identical conditions or to understand interactions at the molecular scale (Bohn et al.,2017). However, they are too simple to study more complex phenomena and the kinetics of food digestion for which dynamic in vitro models are more appropriate (Dupont et al., 2018). There was a high heterogeneity between the different static in vitro digestion models that were used by the research groups all around the world. Models were differing in the pH used in the different phases (gastric and intestinal), their duration, the digestive enzyme/substrate ratio, etc For that reason, comparing results obtained from one study to another was impossible and there was a crucial need for a harmonized method that could be used by everyone allowing comparison between studies. This was one of the main objectives of the INFOGEST COST Action.

Uptake relates to the term bioaccessibility, which is the fraction of a dose that is potentially available for absorption or uptake after digestion. Transcellular uptake can take place via two modes of transport: active and passive. The process of evaluation of digestion and uptake of bio-nanosystems in food containing bioactive compounds starts with the modeling of in vivo characteristics by using in vitro methods. Interactions within the food matrix before and after intake need further understanding to unravel the fate during digestion and absorption. The availability of the interior network for the incorporation of bioactive compounds can potentially increase uptake, absorption, and bioavailability. The rate and extent of lipid digestion also depends on other initial parameters, such as the emulsifier type, oil type and oil content used, and stability under gastrointestinal conditions. The emulsifier type can also have an impact on the interfacial stability upon digestion and permeability across the intestinal barrier.

Food allergy has been on the increase for many years. The prevalence of allergy to different foods varies widely depending on type of food, frequency of consumption and geographic location. Data from the literature suggests that the prevalence of tree nut allergy is of the order of 1% in the general population. Almond is one such tree nut that is frequently eaten in many parts of the world and represents a potential allergenic hazard. Given the need to label products that contain allergens, a number of different methods of direct and indirect detection have been developed. However, in the absence of population-based threshold data, and given that almond allergy is rare, the sensitivity of the required detection is unknown and thus aims as low as possible. Typically, this is less than 1 ppm, which matches the thresholds that have been shown for other allergens. This review highlights the lack of quantitative data on prevalence and thresholds for almonds, which is limiting progress in consumer protection.

Transglutaminase (TG) catalyzes formation of covalent bonds between lysine and glutamine side chains and has applications in manipulation of food structure. Physical properties of a whey protein mixture (SPC) denatured either at elevated pH or by heat-treatment and followed by TG catalyzed crosslinking, have been characterised using dynamic light scattering, size exclusion chromatography, flourescence spectroscopy and atomic force microscopy. The degree of enzymatic crosslinking appeared higher for pH- than for heat-denatured SPC. The hydrophobic surface properties depended on the treatment, thus heating caused the largest exposure of the hydrophobic core of SPC proteins, which was decreased by crosslinking. The particle size of the treated SPC samples increased upon crosslinking by TG. Moreover, the particle morphology depended on the type of denaturing treatment, thus heat-treated SPC contained fibrillar structures, while pH-denatured SPC remained globular as documented by using atomic force microscopy. Finally, the in vitro digestability of the different SPC samples was assessed under simulated gastric and intestinal conditions. Notably heat-treatment was found to lower the gastric digestion rate and enzymatic crosslinking reduced both the gastric and the intestinal rate of digestion. These characteristics of the various SPC samples provide a useful basis for design of isoenergic model foods applicable in animal and human studies on how food structure affects satiety.

The profile of bile acids (BA) largely depends on the enzymatic activity of the microbiota, but this can be modulated by the dietary addition of biologically active compounds, e.g., polyphenols and polyunsaturated fatty acids. The aim of this study was to examine the effect of dietary raspberry pomace as a rich source of biologically active compounds on microbial activity and the BA profile in the caecum of rats fed a high-fat diet. Wistar rats were fed the standard diet AIN-93, a high-fat diet or a modified high-fat diet enriched with 7% different types of processed raspberry pomaces produced by standard grinding and fine grinding, with or without seeds. Rats fed the high-fat diet for 8 weeks showed some disorders in liver function and cecal BA, as manifested by an increased concentration of cholesterol, total BA in the liver and cholic, deoxycholic, and β-muricholic acids in the cecal digesta. In general, irrespective of the type of raspberry pomace, these dietary preparations decreased liver cholesterol, hepatic fibroblast growth factor receptor 4, peroxisome proliferator-activated receptor alpha, cecal ammonia and favorable changed BA profile in the cecum. However, among all dietary pomaces, the finely ground preparation containing seeds had the greatest beneficial effect on the caecum by modulating bacterial activity and reducing the levels of secondary BA.

The present review is aimed at elucidating relatively new aspects of mucoadhesion/mucus interaction and related phenomena that emerged from a Mucoadhesion workshop held in Munster on 2-3 September 2015 as a satellite event of the ICCC 13th-EUCHIS 12th. After a brief outline of the new issues, the focus is on mucus description, purification, and mucus/ mucin characterization, all steps that are pivotal to the understanding of mucus related phenomena and the choice of the correct mucosal model for in vitro and ex vivo experiments, alternative bio/mucomimetic materials are also presented. Then a selection of preparative techniques and testing methods are described (at molecular as well as micro and macroscale) that may support the pharmaceutical development of mucus interactive systems and assist formulators in the scale-up and industrialization steps. Recent applications of mucoadhesive systems (including medical devices) intended for different routes of administration (oral, gastrointestinal, vaginal, nasal, ocular, and intravesical) and for the treatment of difficult to treat pathologies or the alleviation of symptoms are described.

Within the active field of in vitro digestion in food research, the COST Action INFOGEST aimed to harmonize in vitro protocols simulating human digestion on the basis of physiologically inferred conditions. A harmonized static in vitro digestion (IVD) method was recently published as a primary output from this network. To validate this protocol, inter-laboratory trials were conducted within the INFOGEST network. A first study was performed using skim milk powder (SMP) as a model food and served to compare the different in-house digestion protocols used among the INFOGEST members. In a second inter-laboratory study applying the harmonized protocol, the degree of consistency in protein hydrolysis was investigated. Analysis of the hydrolyzed proteins, after the gastric and intestinal phases, showed that caseins were mainly hydrolyzed during the gastric phase, whereas β-lactoglobulin was, as previously shown, resistant to pepsin. Moreover, generation of free amino acids occurred mainly during the intestinal phase.The study also showed that a few critical steps were responsible for the remaining inter-laboratory variability. The largest deviations arose from the determination of pepsin activity. Therefore, this step was further clarified, harmonized, and implemented in a third inter-laboratory study.The present work gives an overview of all three inter-laboratory studies, showing that the IVD INFOGEST method has led to an increased consistency that enables a better comparability of in vitro digestion studies in the future.