Increase In Bioaccessibility Research Articles

Combinatorial Delivery of Docetaxel- and Erlotinib-Loaded Functionalized Nanostructured Lipid Carriers for the Treatment of Triple-Negative Breast Cancer Using Quality-by-Design Approach.

This study explored the combined administration of docetaxel (DOC) and erlotinib (ERL) using nanostructured lipid carriers (NLCs), with folic acid (FA) conjugation to enhance their synergistic anticancer efficacy against triple-negative breast cancer. NLCs were developed through hot melt homogenization-ultrasound dispersion, and optimized by a quality-by-design (QbD) approach using Plackett-Burman design and Box-Behnken design. Plots were generated based on maximum desirability. Spherical, nanosized dispersions (<200 nm) with zeta potential ranging from -16.4 to -14.15 mV were observed. These nanoformulations demonstrated ~95% entrapment efficiency with around 5% drug loading. Stability tests revealed that the NLCs remained stable for 6 months under storage conditions at 4 °C. In vitro release studies indicated sustained release over 24 h, following Higuchi and Korsmeyer-Peppas models for NLCs and FA NLCs, respectively. Additionally, an in vitro pH-stat lipolysis model exhibited a nearly fivefold increase in bioaccessibility compared to drug-loaded suspensions. The DOC-ERL-loaded formulations exhibited dose- and time-dependent cytotoxicity, revealing synergism at a 1:3 molar ratio in MDA-MB-231 and 4T1 cells, with combination indices of 0.35 and 0.37, respectively. Co-treatment with DOC-ERL-loaded FA NLCs demonstrated synergistic anticancer effects in various in vitro assays.

Effect and mechanisms of thermal sterilization methods on the in vitro phenolic bioaccessibility of rose tea with milk

Rose polyphenols, key functional components in roses, require adequate bioaccessibility for their health benefits, subject to influence by food components and processing. Investigating the impact of various thermal sterilization methods on the bioaccessibility of rose polyphenols in rose tea with milk and the underlying mechanisms, our findings indicated a significant increase in bioaccessibility following treatment at 85 °C/30 min. Conversely, 121 °C/15 min treatment decreased bioaccessibility. Examining the interaction between β-casein in milk and rose polyphenols under different sterilization conditions, SEM and particle size analysis revealed binding, with fluorescence spectroscopy indicating non-covalent bonds. Binding forces followed the order 121 °C > 85 °C > 25 °C. Notably, at 85 °C, non-covalent binding improved polyphenol bioaccessibility, while the intensified binding at 121 °C decreased it. SDS-PAGE and amino acid analysis confirmed no covalent bond. This study establishes a theoretical basis for selecting thermal sterilization temperatures for milk-flower combinations, considering polyphenol bioaccessibility.

High-Pressure Processing of Fruit Smoothies Enriched with Dietary Fiber from Carrot Discards: Effects on the Contents and Bioaccessibilities of Carotenoids and Vitamin E.

The effects of high-pressure processing (HPP) (450 MPa/600 MPa/3 min) on the carotenoid and vitamin E contents of smoothies made from strawberry, orange juice, banana and apple, and the same smoothies enriched with dietary fiber from discarded carrots were compared. The contents and bioaccessibilities of these compounds were also evaluated over the course of 28 days at 4 °C. The application of HPP in the formulations significantly increased the contents of β-cryptoxanthin, α-carotene and β-carotene and retained the contents of lutein, zeaxanthin and vitamin E compared to untreated samples. A decreasing trend in the content of each compound was observed with an increase in storage time. The application of HPP initially led to reductions in the bioaccessibility of individual compounds. However, overall, during storage, there was an increase in bioaccessibility. This suggests that HPP influences cell structure, favoring compound release and micelle formation. HPP is a sustainable method that preserves or enhances carotenoid extractability in ready-to-drink fruit beverages. Furthermore, the incorporation of dietary fiber from carrot processing discards supports circular economy practices and enhances the health potential of the product.

Resveratrol-loaded octenyl succinic anhydride modified starch emulsions and hydroxypropyl methylcellulose (HPMC) microparticles: Cytotoxicity and antioxidant bioactivity assessment after in vitro digestion

Hydroxypropyl methylcellulose (HPMC)-based microparticles and modified starch emulsions (OSA-MS) were loaded with resveratrol and characterized regarding their physicochemical and thermal properties. Both delivery systems were subject to an in vitro gastrointestinal digestion to assess the bioaccessibility of resveratrol. In addition, cell-based studies were conducted after in vitro digestion and cytotoxicity and oxidative stress were assessed.HPMC-based microparticles displayed higher average sizes (d) and lower polydispersity index (PDI) (d = 948 nm, PDI < 0.2) when compared to OSA-MS-based emulsions (d = 217 nm, PDI < 0.3). Both proved to protect resveratrol under digestive conditions, leading to an increase in bioaccessibility. Resveratrol-loaded HPMC-microparticles showed a higher bioaccessibility (56.7 %) than resveratrol-loaded emulsions (19.7 %).Digested samples were tested in differentiated co-cultures of Caco-2 and HT29-MTX, aiming at assessing cytotoxicity and oxidative stress, and a lack of cytotoxicity was observed for all samples. Results displayed an increasing antioxidant activity, with 1.6-fold and 1.4-fold increases over the antioxidant activity of free resveratrol, for HPMC-microparticles and OSA-MS nanoemulsions, respectively.Our results offer insight into physiological relevancy due to assessment post-digestion and highlight the protection that the use of micro-nano delivery systems can confer to resveratrol and their potential to be used as functional food ingredients capable of providing antioxidant benefits upon consumption.

Risk reductions during pyrene biotransformation and mobilization in a model plant-bacteria-biochar system

The productive application of motile microorganisms for degrading hydrophobic contaminants in soil is one of the most promising processes in modern remediation due to its sustainability and low cost. However, the incomplete biodegradation of the contaminants and the formation of the intermediary metabolites in the process may increase the toxicity in soil during bioremediation, and motile inoculants may mobilize the pollutants through biosorption. Therefore, controlling these factors should be a fundamental part of soil remediation approaches. The aim of this study was to evaluate the sources of risk associated with the cometabolism-based transformation of 14C-labeled pyrene by inoculated Pseudomonas putida G7 and identify ways to minimize risk. Our model scenario examined the increase in bioaccessibility to a distant source of contamination facilitated by sunflower (Helianthus annuus L.) roots. A biochar trap for mobilized pollutant metabolites and bacteria has also been employed. The experimental design consisted of pots filled with a layer of sand with 14C-labeled pyrene (88 mg kg−1) as a contamination focus located several centimeters from the inoculation point. Half of the pots included a biochar layer at the bottom. The pots were incubated in a greenhouse with sunflower plants and P. putida G7 bacteria. Pots with sunflower plants showed a higher biodegradation of pyrene, its mobilization as metabolites through the percolate and the roots, and bacterial mobilization toward the source of contamination, also resulting in increased pyrene transformation. In addition, the biochar layer efficiently reduced the concentrations of pyrene metabolites collected in the leachates. Therefore, the combination of plants, motile bacteria and biochar safely reduced the risk caused by the biological transformation of pyrene.

Food-to-Food Fortification of a Traditional Pearl Millet Gruel with a Natural Source of β-Carotene (Sweet Potato) Improves the Bioaccessibility of Iron and Zinc

Iron and zinc deficiencies are still a major public health concern in the Far North Region of Cameroon where staple foods are mainly mineral rich cereals which equally contain inhibitors of their bioaccessibility. The effect of food-to-food fortification of a traditional pearl millet gruel with a natural source of β-carotene on the bioaccessibility of iron and zinc was assessed. A sensory evaluation of gruels fortified at 20, 30, and 40% with mashed sweet potato was carried out. The samples were analysed for carotenoids, phytates, polyphenols, iron, and zinc contents. Bioaccessible iron and zinc were evaluated using in vitro digestion method. The gruel fortified at 20% with mashed sweet potato had better scores ( P &lt; 0.05) of taste (3.93), colour (3.36), and overall acceptability (3.80) compared to the control. Carotenoid, polyphenol, and phytate contents were higher in fortified gruels ( P &lt; 0.05) compared to the control, while iron and zinc contents were lower. A significant increase ( P &lt; 0.05) in bioaccessibility of 8.08% and 26.96% for iron and 53.79% and 62.92% for zinc was observed at 20 and 30% incorporation level, respectively. However, at 40% incorporation level, the increase in bioaccessible iron was less important and bioaccessible zinc decreased. Mashed sweet potato can be used as a fortificant to improve the bioaccessibility of iron and zinc contents of local pearl millet gruel, if added moderately.

Development of carboxymethyl chitosan-coated zein/soy lecithin nanoparticles for the delivery of resveratrol.

The objective of this work is to formulate a zein-based nanocomposite for the delivery of natural polyphenols. A proprietary atomizing/antisolvent precipitation (AAP) process was used to prepare carboxymethyl chitosan (CMC)-coated zein/soy lecithin (SL) nanoparticles (ZLC NPs). At a suitable mass ratio of zein/SL/CMC (100 : 30 : 30), ZLC NPs with desirable redispersibility and physicochemical stability were successfully fabricated. After that, resveratrol (Res) as the representative natural polyphenol was encapsulated in ZLC NPs. The optimized Res/ZLC NPs exhibited a spherical morphology, small size (259.43 ± 2.47 nm), large zeta potential (-47.7 ± 0.66 mV), and high encapsulation efficiency (91.32 ± 4.01%) and loading capacity (5.27 ± 0.35%). Further characterization indicated that Res was encapsulated in the hydrophobic core of the ZLC matrix in an amorphous state. Compared to free Res, Res/ZLC NPs showed a 2.55-fold increase in the Res dissolution rate, a 2.27-fold increase in bioaccessibility, and a 1.69-fold increase in ABTS˙+ scavenging activity. Also, Res/ZLC NPs showed a higher Res retention rate (>68.0%) than free Res (<35.0%) over 45 days of storage. Therefore, ZLC NPs have promising potential as vehicles for natural polyphenols.

Improving the bioaccessibility of lipophilic ingredient in its oral intestinal delivery by ultrasound and biological cross-linker.

Great efforts have been made to improve the oral bioaccessibility of lipophilic ingredients with multi-functionalities. Achieving intestinal delivery of lipophilic ingredients and their encapsulation in micelles composed of bile salts and lipid hydrolysates (i.e. fatty acids) is critical for improving oral bioaccessibility. Therefore, oil-core microcapsules are considered ideal carriers of lipophilic ingredients. Previous studies have reported oil-core/zein-shell microcapsules constructed by a one-step anti-solvent process. Still, its efficacy as an intestinal delivery system was limited because if the porous shell structure. Zein solution was pretreated with ultrasound and tannic acid (TA) cross-linking. Composite oil-core microcapsule (COM) with a compact shell structure was successfully prepared by using modified zein solution in the anti-solvent process. Fourier-transform infrared spectroscopy and circular dichroism analyses indicated that ultrasound and TA synergistically promote the conformational transition of zein from α-helix to β-sheet and enhance the hydrophobic interactions among protein chains. The above changes contribute to the strengthen of shell zein network. Correspondingly, COM presents superior encapsulation efficiency and environmental stability over the simple oil-core microcapsule (SOM) prepared without the use of ultrasound and TA. Furthermore, antioxidant activity of β-carotene was well retained during the encapsulation process. In vitro studies indicated that COM was more resistant to digestibility and acid-induced swelling. More than 87% of β-carotene could be released in the intestine in a sustainable way. The controllable release behavior thus promoted a significant increase in bioaccessibility of β-carotene encapsulated in COM compared to SOM (85.9% versus 48.5%). The COM generated here shows potential for bioaccessibility improvement of lipophilic ingredients. © 2022 Society of Chemical Industry.

Effect of agitation and added cholesterol esterase on bioaccessibility of phytosterols in a standardized in vitro digestion model

There is great interest in reaching a consensus method for in vitro digestion of foods. The COST INFOGEST network of researchers has developed a standardized protocol, which is appropriate for basic digestibility studies, but may be insufficient for more complex studies, such as micronutrient bioaccessibility. In the present study, the bioaccessibility of phytosterols (PS) was evaluated using the standardized and modified versions of the in vitro digestion protocol. The INFOGEST protocol was used without modification for 2% solutions of either free phytosterols (FPS) or esterified phytosterols (EPS) in soybean oil. The effect of two variables which have yet to be explored using the INFOGEST protocol was subsequently evaluated. Those variables are: (1) changing the mode of agitation from orbital shaking to head over heels (HOH) rotation and (2) adding pancreatic cholesterol esterase (CE) during the intestinal phase. Bioaccessibility of FPS was greater than that of EPS, and HOH rotation caused a further increase in bioaccessibility of FPS but not EPS. Addition of CE caused a slight, but significant improvement in bioaccessibility of EPS, though hydrolysis was incomplete. Our findings highlight a need for further evaluation of the standardized in vitro digestion protocol, especially for complex studies such as lipid bioaccessibility.

The Effects of Food on Cannabidiol Bioaccessibility.

Cannabidiol (CBD) is a hydrophobic non-psychoactive compound with therapeutic characteristics. Animal and human studies have shown its poor oral bioavailability in vivo, and the impact of consuming lipid-soluble CBD with and without food on gut bioaccessibility has not been explored. The purpose of this research was to study the bioaccessibility of CBD after a three-phase upper digestion experiment with and without food, and to test lipase activity with different substrate concentrations. Our results showed that lipase enzyme activity and fatty acid absorption increased in the presence of bile salts, which may also contribute to an increase in CBD bioaccessibility. The food matrix used was a mixture of olive oil and baby food. Overall, the fed-state digestion revealed significantly higher micellarization efficiency for CBD (14.15 ± 0.6% for 10 mg and 22.67 ± 2.1% for 100 mg CBD ingested) than the fasted state digestion of CBD (0.65 ± 0.7% for 10 mg and 0.14 ± 0.1% for 100 mg CBD ingested). The increase in bioaccessibility of CBD with food could be explained by the fact that micelle formation from hydrolyzed lipids aid in bioaccessibility of hydrophobic molecules. In conclusion, the bioaccessibility of CBD depends on the food matrix and the presence of lipase and bile salts.

New Insights into Health Risk Assessments for Inhalational Exposure to Metal(loid)s: The Application of Aqueous Chemistry Modelling in Understanding Bioaccessibility from Airborne Particulate Matter

Aqueous modelling of chemical speciation in simulated lung fluid (SLF) enables a better understanding of the underlying chemical factors that influence metal(loid) inhalation bioaccessibility from airborne particulate matter. Such an approach can be used to supplement experimental techniques that are integral to the health risk assessment of metal(loid) exposure by inhalational routes. In this paper, we modelled the aqueous chemistry of airborne particulate-bound metal(loid)s (As, Cu, Mn, Pb and Zn) in a SLF based on Gamble’s solution (neutral pH). The modelling was performed using two software packages (Geochemist’s Workbench 14 and OLI Studio 9.5) and a total of five thermochemical databases (GWB Thermo, MINTEQ, PHREEQC, WATEQ4F and the default database for OLI Studio). Modelled results were compared with experimentally determined bioaccessibilities for the NIST 2710a standard reference material (SRM) and with literature-reported bioaccessibilities for NIST 1648a and BCR 038 SRMs. Whilst the models correctly describe the observed increase in bioaccessibility for more dilute solid/liquid extraction ratios, the performance of the models against the fractional bias of the mean (FBmean) and the normalised mean square error (NMSE) statistical metrics was generally outside the acceptance criteria. Findings from an analysis of the main aqueous chemical species predicted to be present in SLF indicate that carbonate and chloride complexes of Cu, Mn, Pb and Zn predominate, whilst free cations (for Cu, Mn and Zn) and hydroxides (for Cu) also play a role in solubilisation. Arsenic is not predicted to form significant complexes with the SLF components and is present in solution mainly as the HAsO42− ion and its conjugate acid, H2AsO4−. For modelled runs where glycine and citrate were present, significant increases in the bioavailability of Cu and Zn were predicted as a result of complexation with these ligands. An additional finding from our experimental bioaccessibility results for NIST 2710a was that the inclusion of the lung fluid surfactant dipalmitoylphosphatidylcholine (DPPC) in the SLF did not significantly affect the bioaccessibility. Our study provides useful insights into the likely aqueous- and solid-phase speciation of metal(loid)s in SLF and highlights that future developments in this area should consider the role of mineralogy and surface interactions.

Cell disruption of Nannochloropsis sp. improves in vitro bioaccessibility of carotenoids and ω3-LC-PUFA

The incorporation of microalgae into processed food products is considered a sustainable strategy to enrich food products in omega-3 long chain polyunsaturated fatty acids (ω3-LC-PUFA). However, the microstructural properties of the microalgae might influence the nutrient digestibility and bioaccessibility during consumption. The current study proved the importance of cell disruption of Nannochloropsis sp. for the in vitro lipid digestibility and bioaccessibility of ω3-LC-PUFA and carotenoids. While an incomplete lipid digestion and low bioaccessibility values (1–6% for carotenoids and 13% for ω3-LC-PUFA) were observed for untreated biomass, cell disruption by high pressure homogenization resulted in a complete lipid digestibility and a threefold increase in bioaccessibility. It was shown that the Nannochloropsis sp. cell wall and/or cell membrane act as a natural barrier for (lipophilic) nutrients during in vitro digestion. Hence, microalgal cell disruption is a crucial step in the design of healthy food products enriched with microalgae.

Bioavailability and Bioactivity of Encapsulated Phenolics and Carotenoids Isolated from Red Pepper Waste.

In order to deactivate the health properties of bioactive compounds, they need to withstand the effects of food processing, their potential release from the food matrix, and remain bio-accessible in the gastrointestinal tract. Bio-actives from different plants are prone to oxidative degradation, and encapsulation is an effective method in improving their stability. In the present study, red pepper waste (RPW), a by-product of vegetable processing industry, was encapsulated in whey protein using spray and freeze-drying techniques. The aim was to evaluate the effects of in vitro gastrointestinal digestion on the release and bioactivity of encapsulated bio-actives, after each digestion step. The results showed that the release of phenolics and carotenoids, as well as antioxidants, anti-hyperglycemic, and anti-inflammatory activities are influenced by pH and intestinal fluid, with pH 7.5 exhibited at higher levels. There was a rapid initial release of carotenoids from whey protein matrices, while a more gradual increase of phenolics was observed, reaching around 50% for both encapsulates first at 6 h and 37 °C, and small intestine conditions. The encapsulation of RPW demonstrated a protective effect against pH changes and enzymatic activities along digestion, and contributed to the increase in bio-accessibility in the gut. Also, the results suggest that encapsulation is an efficient method for valorization of bio-actives from RPW, with improvements in nutrition, color, and bioactive properties.

Solubility, stability, and bioaccessibility improvement of curcumin encapsulated using 4-α-glucanotransferase-modified rice starch with reversible pH-induced aggregation property

Curcumin is a polyphenolic compound with anti-cancer, anti-inflammatory and anti-oxidant effects. However, its application in the food industry is very limited owing to its low water solubility and chemical stability. In the present study, 4αGTase-treated rice starch (GS) was prepared by treating rice starch with 4-α-glucanotransferase (4αGTase) for 1 h (1 GS) and 96 h (96 GS), and the physicochemical properties of GS were analyzed. Moreover, the capability of GS to improve the encapsulation efficiency and stability of curcumin by forming complexes was investigated in comparison with maltodextrin (MD) and β-cyclodextrin (CD). GS is known to contain cyclic glucans and amylopectin clusters that contribute to its complex forming capability with bioactive compounds. Upon encapsulation with 1 GS and 96 GS, curcumin solubility increased by 2,241- and 2,846-fold, respectively. UV stability of the encapsulated curcumin with 96 GS also improved by 1.83-fold. GS was effective under all pH conditions except for 96 GS under acidic condition, as well as curcumin encapsulated with 1 GS and 96 GS exhibited 11.53- and 11.27-fold increase in bioaccessibility. The increased stability of curcumin within GS may be attributed to the unique molecular structure of GS interacting with curcumin, as suggested by chromatography and Fourier transform infrared spectroscopy. Also, the improved bioaccessibility of curcumin encapsulated with 96 GS even with lower pH stability at acidic pH seems to be partly attributed to reversible pH-induced aggregation of 96 GS. These results suggest that GS could act as a novel food-grade host material to improve the chemical stability of curcumin.

The Effect of Sodium Carboxymethylcellulose on the Stability and Bioaccessibility of Anthocyanin Water-in-Oil-in-Water Emulsions

Water-in-oil-in-water (W1/O/W2) emulsions provide protective encapsulation to plant bioactive compounds in food matrix and under gastrointestinal conditions. However, the stability of the emulsions during the storage is crucial for their use in the food industry. Hence, the aim of this study was to enhance the stability and bioaccessibility of W1/O/W2 emulsions containing anthocyanins with the use of sodium carboxymethylcellulose (CMCNa). The emulsions were prepared by ultrasound technology, adding polyglycerol polyricinoleate (PGPR) in the inner aqueous phase of emulsions, and lecithin and Tween 20 in the outer aqueous phase. The systems were physicochemical characterized over the time and their behavior under simulated gastrointestinal conditions was investigated. Our results showed high encapsulation efficiencies above 90% and an increase in bioaccessibility with the use of CMCNa. Moreover, the polymer addition slowed down the free fatty acid release and increased the oil digestibility of lecithin-stabilized emulsions. These latter emulsions presented the highest bioaccessibility (31.08 ± 1.73%), the more negative values of ζ-potential and no variations on the particle size and the backscattering profile over the time, thus being the most stable emulsions. These results provide useful information for the design of anthocyanin emulsion-based delivery systems to guarantee their functionality in food matrices as well as through the gastrointestinal tract.

Influence of freezing on the bioaccessibility of beetroot (Beta vulgaris) bioactive compounds during in vitro gastric digestion.

The effect of freezing (in liquid nitrogen at -196 °C , at -80 °C and at -20 °C) on the food matrix structure and the consequent effect on the bioaccessibility of total polyphenol content (TPC) and antioxidant activity (AA) of beetroot was investigated by an in vitro digestion method. The in vitro digestion involved incubation in simulated saliva followed by incubation in simulated gastric juice. Bioaccessibility of bioactive compounds was evaluated by measuring the TPC and the AA during in vitro digestion in both the beetroot matrix and the gastric juice. Release of TPC and AA of beetroot was higher in frozen samples (55 ± 5% for TPC and 68 ± 5% for AA) than in the fresh beetroot sample (∼46% for TPC and ∼53% for AA). The mass transfer kinetics were described by using a Weibull model with mean relative errors lower than 8.5% contributing to a better understanding of the influence of freezing on the bioaccessibility of bioactive compounds. From the treatments tested in this study, freezing with liquid nitrogen resulted in the greatest increase in bioaccessibility of the antioxidant and phenolic compounds of beetroots. © 2018 Society of Chemical Industry.

In Vitro Bioaccessibility of Carotenoids and Vitamin E in Rosehip Products and Tomato Paste As Affected by Pectin Contents and Food Processing.

Limited bioavailability of antioxidants present in food from fruits and vegetables matrices is determined by their low bioaccessibility due to the physical and chemical interactions of the antioxidants with the indigestible polysaccharides of cell walls. Therefore, this in vitro investigation aimed to assess the bioaccessibility of carotenoids and vitamin E from rosehips as well as from tomato paste and to investigate several aspects of effects of pectin contents and food processing on bioaccessibility. Following the addition of the enzyme mixture Fructozym P6-XL, the bioaccessibility of carotenoids from rosehips as well as from tomato paste significantly increased. The average relative increase in bioaccessibility from rosehips was lower for ( all-E)-β-carotene compared with ( all-E)-lycopene and ( all-E)-rubixanthin. In contrast, increases of bioaccessibility of α-tocopherol were comparable for rosehip samples and tomato paste.

Enhancement of lycopene bioaccessibility from tomato juice using excipient emulsions: Influence of lipid droplet size

The use of excipient emulsions to increase the bioaccessibility of lycopene in tomato juice was studied by simulating gastrointestinal conditions. The influence of droplet diameter (d=0.17 or 19μm) and thermal treatment (90°C, 10min) on lycopene bioaccessibility was evaluated. Lycopene bioaccessibility was relatively low (<8%) in the absence of excipient emulsions due to the crystalline nature of the carotenoids and their entrapment within chromoplasts. Emulsions containing small droplets were fully digested within the small intestine phase, and led to a higher bioaccessibility (12.5%) than emulsions containing large droplets (10.0%) or emulsion-free samples (7.5%). The relatively modest increase in bioaccessibility was attributed to the high level of entrapment in crystalline form. Thermal processing did not appreciably disrupt tomato cells, and therefore only led to a slight increase in lycopene bioaccessibility. Overall, this study shows that excipient emulsions may increase the bioaccessibility of carotenoids in tomato juices.

Increased bioavailability of celecoxib under fed versus fasted conditions is determined by postprandial bile secretion as demonstrated in a dynamic gastrointestinal model

The objective of this study was to utilize physiologically relevant dynamic dissolution testing with the TNO intestinal model (TIM-1) in vitro gastrointestinal model to investigate the bioaccessibility of celecoxib. A single 200-mg dose of celecoxib was evaluated under average adult human physiological conditions simulated in the TIM-1 system. The in vitro data were compared with the clinically established pharmacokinetic data. When expressed as a percent of drug that progresses from the duodenum to the jejunum and ileum compartments (bioaccessible sites), the study demonstrated a 2-fold increase in the total bioaccessibility for celecoxib when co-administered with a high-fat meal as opposed to co-administration with a glass of water (fasted conditions). That increase in bioaccessibility was similar to a 1.2 to 1.6-fold increase in systemic exposure in adults and children following co-administration with a high-fat meal when compared to the exposure measured when celecoxib was co-administered with only water. Following that comparison, the flexibility of the TIM-1 system was used to more specifically investigate individual parameters of gastrointestinal conditions, such as the rate of bile secretion (emptying of the bile bladder) that accompanies high-fat meal consumption. We demonstrated that increased bile secretion after co-administration of a high-fat meal played a more important role in the increased celecoxib bioaccessibility than did the food matrix. This indicates that in humans without a bile bladder the exposure of celecoxib administered with food might be as low as under fasted state.

The Type and Concentration of Milk Increase the in Vitro Bioaccessibility of Coffee Chlorogenic Acids

Coffee with different types and concentrations of milk was digested with pepsin (2 h) and pancreatin (2 h) to simulate gastropancreatic digestion. Chlorogenic acids (CGAs) were determined by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry in ultrafiltrate (cutoff 3 kDa) to evaluate their bioaccessibility. After digestion, bioaccessible CGAs decreased from 80.2 to 53.0 and 69.5 μmol/200 mL in coffee without milk and coffee-whole milk, respectively. When whole, semiskimmed, skimmed, or diluted milk were present, the increase in bioaccessibility was dependent on fat content (r = 0.99, p < 0.001). No relationship was observed between bioaccessibility and proteins, carbohydrates, and calcium content. The addition of milk to coffee caused an immediate decrease in the bioaccessibility due to CGAs binding to proteins. After digestion, 86-94% of bound CGAs remained in the high molecular weight fraction. Casein bound 5-caffeoylquinic acid with high affinity (K(D) of 37.9 ± 2.3 μmol/L; n = 0.88 ± 0.06).