Simulated Gastric Conditions Research Articles

Potential Probiotic Enterococcus faecium OV3-6 and Its Bioactive Peptide as Alternative Bio-Preservation.

Probiotic Enterococcus faecium OV3-6 and its secreted active peptide were characterized and investigated. The strain survived in simulated gastric and small intestinal conditions at 88.16% and 94.33%, respectively. The safety assessment revealed that the strain was shown α-hemolysis and susceptible to most clinically relevant antibiotics, but intermediate sensitivity to erythromycin and kanamycin was found. It does not harbor any virulence genes except for the efaAfm gene. Both of its living cells and the cell-free supernatants (CFS) of the strain significantly reduced the adhesion of E. coli and S. Typhi on Caco-2 cells. The strain can regulate the secretion of pro and inflammatory cytokines, IL-6 and IL-12 and induce the secretion of anti-inflammatory IL-10 of the Caco-2 cell. The strain can prevent the growth of Gram-positive strains belonging to the genera Bacillus, Carnobacterium, Listeria, and Staphylococcus. It also presented the entP gene that involves the production of bacteriocin named enterocin P. The antimicrobial peptide was matched 40% with 50S ribosomal proteins L29 (7.325 kDa), as revealed by LC-MS/MS. This active peptide exhibits heat stability, is stable over a wide pH range of 2−10, and maintains its activity at −20 and 4 °C for 12 weeks of storage. Altogether, E. faecium OV3-6 thus has potential for consideration as a probiotic and bio-preservative for applied use as a fermented food starter culture and in functional food or feed industries.

Encapsulation of hydrophobic capsaicin within the aqueous phase of water-in-oil high internal phase emulsions: Controlled release, reduced irritation, and enhanced bioaccessibility

Capsaicin (CAP) is a hydrophobic substance with various physiological effects in chili peppers that is responsible for their perceived heat. Nonetheless, its application as a nutraceutical is hugely hindered by its low bioaccessibility and mucosal irritation. In this study, capsaicin was entrapped in the water phase of water-in-oil (W/O) high internal phase emulsions (HIPEs) using a pH-driven method. Initially, the capsaicin was mixed with sodium alginate (SA) to form a water-dispersible form of the capsaicin and then used to form CAP-loaded W/O HIPEs. The influence of capsaicin concentration on the properties of W/O HIPEs was then investigated. Cryo-SEM observation demonstrated a thick lipid shell formed around the water droplets and a dense network in the aqueous core. The addition of capsaicin caused an increase in the viscoelasticity of the HIPEs. The CAP-loaded HIPEs exhibited good stability and the capsaicin was shown to remain within the aqueous core (rather that moving to the oil phase) during storage. Only a relatively small amount of capsaicin leaked out of the HIPEs under simulated oral and gastric conditions, but it was progressively released under simulated small intestine conditions as the external lipid phase was digested by lipase. The bioaccessibility of capsaicin was greatly enhanced after encapsulation. An animal experiment showed that the CAP-loaded HIPEs reduced the irritation of the gastric mucosa. Our results suggest that W/O HIPEs may be a useful delivery system for active ingredients with undesirable flavor profiles and low bioaccessibilities.

In Vitro and In Vivo Assessment of the Potential of Escherichia coli Phages to Treat Infections and Survive Gastric Conditions.

Enterotoxigenic Escherichia coli (ETEC) and Shigella ssp. infections are associated with high rates of mortality, especially in infants in developing countries. Due to increasing levels of global antibiotic resistance exhibited by many pathogenic organisms, alternative strategies to combat such infections are urgently required. In this study, we evaluated the stability of five coliphages (four Myoviridae and one Siphoviridae phage) over a range of pH conditions and in simulated gastric conditions. The Myoviridae phages were stable across the range of pH 2 to 7, while the Siphoviridae phage, JK16, exhibited higher sensitivity to low pH. A composite mixture of these five phages was tested in vivo in a Galleria mellonella model. The obtained data clearly shows potential in treating E. coli infections prophylactically.

Emulsion acid colloidal stability and droplet crystallinity modulate postprandial gastric emptying and short-term satiety: a randomized, double-blinded, crossover, controlled trial in healthy adult males

Emulsion droplet triacylglycerol (TAG) crystallinity and colloidal stability can alter the postprandial metabolism, although evidence of their interactive effects is limited. This acute meal crossover study investigated the influences of droplet TAG crystallinity at 37°C and colloidal gastric stability on gastric emptying (GE), acute lipemia, and satiety. We gave 15 healthy adult males (mean±SD age, 24.9 y±4.5 y; BMI, 26.0 kg/m2±2.0 kg/m2; fasting TAG, 0.9mmol/L ±0.3 mmol/L) 250 mL of four 20% palm stearin or palm olein emulsions with similar particle size distributions and containing partially crystalline droplets that remained stable (SS) or destabilized (SU) or containing liquid droplets that remained stable (LS) or destabilized (LU) when exposed to simulated gastric conditions. Baseline and 6-h postprandial ultrasound gastric antrum measurements, satiety visual analogue scales (VAS), and blood samples for analyses of plasma TAG, peptide YY (PYY), glucagon-like peptide-1 (GLP-1), ghrelin, leptin, glucose-dependent insulinotropic polypeptide, insulin, and glucose were collected. Changes from baseline and incremental area under the curve (iAUC) values were analyzed by repeated-measures ANOVA. TAG responses did not differ significantly. The gastric antrum area decreased faster (P≤0.01) after treatment with the acid-unstable emulsions (SU and LU), and satiety VAS ratings and plasma endpoints differed between treatments. After LS treatment, participants had 65% and 59% lower 3-h iAUC values for hunger (P=0.021) and desire to eat (P=0.031), respectively, compared to after SU treatment. LS treatment resulted in higher 6-h iAUC values for ghrelin (141%; P=0.023) and PYY (150%; P=0.043) compared to SU treatment, and LS treatment also resulted in higher GLP-1 values compared to SU (38%; P=0.016) and LU (76%; P=0.001) treatment. Emulsion acid colloidal stability, independent of TAG physical state, delayed GE, and satiety was enhanced after consuming acid stable emulsions containing TAG in the liquid state. The study was registered at clinicaltrials.gov as NCT03990246.

Chemical Changes of Hydroperoxy-, Epoxy-, Keto- and Hydroxy-Model Lipids under Simulated Gastric Conditions.

Chemical changes occurring in dietary lipid oxidation compounds throughout the gastrointestinal tract are practically unknown. The first site for potential chemical modifications is the stomach due to the strong acidic conditions. In this study, model lipids representative of the most abundant groups of dietary oxidation compounds were subjected to in vitro gastric conditions. Thus, methyl linoleate hydroperoxides were used as representative of the major oxidation compounds formed in food storage at low and moderate temperatures. Methyl 9,10-epoxystearate, 12-oxostearate and 12-hydroxystearate were selected as model compounds bearing the oxygenated functional groups predominantly found in oxidation compounds formed at the high temperatures of frying. Analyses were performed using gas-liquid chromatography/flame ionization detection/mass spectrometry and high performance-liquid chromatography/ultraviolet detection. Losses of methyl 9,10-epoxystearate and linoleate hydroperoxides in the ranges 17.8–58.8% and 42.3–61.7% were found, respectively, whereas methyl 12-oxostearate and methyl 12-hydroxystearate remained unaltered. Although quantitative data of the compounds formed after digestion were not obtained, methyl 9,10-dihydroxystearate was detected after digestion of methyl 9,10-epoxystearate, and some major volatiles were detected after digestion of linoleate hydroperoxides. Overall, the results showed that significant modifications of dietary oxidized lipids occurred during gastric digestion and supported that the low pH of the gastric fluid played an important role.

Effect of Alginate-Microencapsulated Hydrogels on the Survival of Lactobacillus rhamnosus under Simulated Gastrointestinal Conditions.

Thanks to the beneficial properties of probiotic bacteria, there exists an immense demand for their consumption in probiotic foods worldwide. Nevertheless, it is difficult to retain a high number of viable cells in probiotic food products during their storage and gastrointestinal transit. Microencapsulation of probiotic bacteria is an effective way of enhancing probiotic viability by limiting cell exposure to extreme conditions via the gastrointestinal tract before releasing them into the colon. This research aims to develop a new coating material system of microencapsulation to protect probiotic cells from adverse environmental conditions and improve their recovery rates. Hence, Lactobacillus rhamnosus was encapsulated with emulsion/internal gelation techniques in a calcium chloride solution. Alginate–probiotic microbeads were coated with xanthan gum, gum acacia, sodium caseinate, chitosan, starch, and carrageenan to produce various types of microcapsules. The alginate+xanthan microcapsules exhibited the highest encapsulation efficiency (95.13 ± 0.44%); they were simulated in gastric and intestinal juices at pH 3 during 1, 2, and 3 h incubations at 37 °C. The research findings showed a remarkable improvement in the survival rate of microencapsulated probiotics under simulated gastric conditions of up to 83.6 ± 0.89%. The morphology, size, and shape of the microcapsules were analyzed using a scanning electron microscope. For the protection of probiotic bacteria under simulated intestinal conditions; alginate microbeads coated with xanthan gum played an important role, and exhibited a survival rate of 87.3 ± 0.79%, which was around 38% higher than that of the free cells (49.4 ± 06%). Our research findings indicated that alginate+xanthan gum microcapsules have a significant potential to deliver large numbers of probiotic cells to the intestines, where cells can be released and colonized for the consumer’s benefit.

Characterisation and functional roles of a highly branched dextran produced by a bee pollen isolate Leuconostoc mesenteroides BI-20

Lactic Acid Bacteria (LAB) from different niches can be responsible for the production of distinct exopolysaccharides (EPS) that might possess important structural and technological features. In this respect, the aim of this study was to isolate an EPS producer LAB strain from bee pollen environment. Leuconostoc mesenteroides BI-20 with a slimy-mucoid colony morphology was identified from bee pollen and the structural, technological and functional characteristics of EPS produced by this strain were determined. EPS BI-20 was a highly branched dextran containing 20% (1 → 3)-linked α-D-glucose branches determined by 1H and 13C NMR analysis. The presence of (1 → 6)/(1 → 3)-linked α-D-glucose linkages in dextran BI-20 was also confirmed by FTIR analysis. Dextran BI-20, with a molecular weight of 1 × 108 Da, possessed strong thermal properties, amorphous nature and highly branched and fibrous microstructural characteristics determined by DSC, TGA, XRD and SEM analysis, respectively. In terms of functional roles, dextran BI-20 demonstrated strong antioxidant capacity detected by ABTS and CUPRAC tests. Finally, no digestion was observed in dextran BI-20 under simulated gastric conditions. Results of this study unveiled techno-functional characteristics of dextran BI-20 produced by a bee pollen isolate LAB strain.

Preparation and Characterization of a Lutein Solid Dispersion to Improve Its Solubility and Stability.

Lutein has been used as a dietary supplement for the treatment of eye diseases, especially age-related macular degeneration. For oral formulations, we investigated lutein stability in artificial set-ups mimicking different physiological conditions and found that lutein was degraded over time under acidic conditions. To enhance the stability of lutein upon oral intake, we developed enteric-coated lutein solid dispersions (SD) by applying a polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF), through a solvent-controlled precipitation method. The SD were characterized in crystallinity, morphology, and drug entrapment. In the dissolution profile of lutein SD, a F80 formulation showed resistance toward the acidic environment under simulated gastric conditions while exhibiting a bursting drug release under simulated intestinal conditions. Our results highlight the potential use of HPMCAS-LF as an effective matrix to enhance lutein bioavailability during oral delivery and to provide novel insights into the eye-care supplement industry, with direct benefits for the health of patients.

Reducing antigenicity of β-lactoglobulin, probiotic properties and safety evaluation of Lactobacillus plantarum AHQ-14 and Lactobacillus bulgaricus BD0390

Probiotics are important bacteria because they are beneficial to human health. Two lactic acid bacteria (LAB) strains capable to hydrolyze immuno-reactive β-lactoglobulin (β-Lg) proteins in milk, including AHQ-14 isolated from Chinese Xinjiang district traditional dairy products and identified as Lactobacillus plantarum by 16S rRNA gene sequences analysis, and Lactobacillus bulgaricusBD0390 kindly donated by Bright Dairy Company (Shanghai, China), were investigated for their probiotic traits and safety. Lactobacillus plantarumAHQ-14 and Lactobacillus bulgaricusBD0390 were tested their ability to lower β-Lg antigenicity, bile salt hydrolase (BSH) activity, survival rate in gastrointestinal and adhesion capacity to HT-29 cells. For preliminary safety assessment, L.plantarumAHQ-14 and L.bulgaricusBD0390 were tested for hemolytic activity, biogenic amines (BAs) production and for their antibiotic resistance. Results showed that L.plantarumAHQ-14 and L.bulgaricusBD0390 were γ-hemolytic and showed high abilities to adhere to HT-29 cells. They exhibited higher survival rates than the control (Lactobacillus rhamnosusGG) under simulated gastric conditions. Both strains produced a small amount of BAs, similar to or even lower than the BAs content in the regularly consumed foods. Furthermore, they showed sensitivity towards conventionally used antibiotics. In conclusion, L.plantarumAHQ-14 and L.bulgaricusBD0390 possessed good characteristics as potential probiotic for functional fermented food in the future.

Lactobacillus fermentum strains with significant probiotic and antioxidant potential

The growing demand for dairy products amended with probiotics has led to the exploration of new beneficial microorganisms such as probiotics with beneficial properties. In the present work, the probiotic and antioxidant potential of Lactobacillus fermentum strains isolated from dairy products were evaluated. Strains were investigated for their probiotic properties by performing different tests such as survival in pepsin, low pH, and bile salt, antibacterial activity, and antioxidant potential. These strains were further evaluated for their utilisation in yogurt formation as a probiotic. The isolated strains were identified as L. fermentum Y1, L. fermentum Y2, and L. fermentum C by 16S rRNA sequencing. All strains showed greater survival ability in simulated gastric conditions (pH 2.2 + pepsin) and in the presence of 0.3% bile salt. The highest antibacterial activity was exhibited by L. fermentum Y1 against Bacillus cereus. Among these three strains, L. fermentum Y1 had the highest reducing power, and L. fermentum C had the highest DPPH scavenging activity. All Lactobacillus strains as a single inoculum or in consortium showed significant (p < 0.05) probiotic properties by maintaining pH, titratable acidity, solid content, and high water holding capacity in comparison to the control in the cow yogurt and homogenised milk. The isolated Lactobacillus strains may be a potential source of probiotics in commercial yogurt preparation.

Development of pelleted feed containing probiotic Lactobacillus rhamnosus GG and Jerusalem artichoke for Nile Tilapia and its biocompatibility studies.

Growth performance and immune systems of tilapias could be improved by Lactobacillus rhamnosus GG (LGG) and Jerusalem artichoke. This research aimed to determine the effects of Jerusalem artichoke on LGG viability after drying and pelleting and their subsequent exposure to simulated gastrointestinal conditions. Fresh LGG cells were added into wall material solutions, including alginate (AL), alginate + milk powder (AM), and alginate + milk powder + Jerusalem artichoke at different concentrations (AMJ). The solutions were then spray dried to obtain LGG powders. The powder with the highest cell number was then selected to mix with tilapia feed mash and pelleted using a nonthermal feed extruder to obtain pelleted feed containing LGG and Jerusalem artichoke. The LGG viability spray dried powders and pelleted feed were analyzed for their cell counts after drying and after exposure to simulated gastrointestinal conditions. The result showed that the number of viable cells in AMJ was significantly higher than AM and AL after drying. The number of viable cells under both simulated gastric and bile salt fluids was improved with the increasing of Jerusalem artichoke concentrations. The number of viable cells after pelleting process could be maintained. LGG in the pelleted feed could also survive under the simulated gastric and bile salt conditions. The study indicates that JA enhanced LGG viability after drying and exposure to simulated gastrointestinal conditions. The pelleted feed containing LGG and Jerusalem artichoke could be applied in tilapia farming, providing convenience to the farmers, and valuable effects to the fish.

A Toolbox for Mimicking Gastrointestinal Conditions in Children: Simulated Paediatric Breakfast Media (SPBM) for Addressing the Variability of Gastric Contents After Typical Paediatric Breakfasts

Since co-administration of dosage forms with food can impact drug exposure, food effect studies became an integral part of oral drug product development. Studies are usually performed in healthy adults and the dosage form is co-administered with a high-fat high-calorie standard breakfast meal to mimic worst-case dosing conditions. A corresponding study design for children is lacking but would be essential for a proper risk-assessment in this vulnerable patient group. To protect healthy children from unnecessary in vivo studies, it would be even more desirable to predict food effects based on other than in vivo studies in the target age group. In the present study, typical children's breakfasts in different parts of the world were identified, prepared and physicochemical properties were assessed. Subsequently, Simulated Paediatric Breakfast Media (SPBM) resembling breakfast composition and properties were designed and applied in in vitro dissolution experiments mimicking the initial composition of the postprandial stomach after breakfast ingestion. Study results indicate the impact of different simulated gastric conditions on drug release. SPBM enabled to better estimate the variability of in vivo drug release in fed dosing conditions and their use will aid in better assessing food effects in children in different parts of the world.

In silico modelling of apo-lactoferrin under simulated gastric conditions: Structural dynamics, binding with β-lactoglobulin and α-lactalbumin, and functional implications

This study employs computational techniques to investigate whether the inclusion of β-lactoglobulin and α-lactalbumin can enhance the molecular stability of apo-lactoferrin in conditions of gastric pH. Atomistic molecular dynamics simulations reveal that acidic pH results in weakened interactions between lactoferrin and the other proteins compared to those under neutral pH. Nevertheless, protein-protein dissociation free energy calculations using the umbrella sampling calculations confirm that some contacts are maintained between apo-lactoferrin and the other whey proteins, specifically the β-lactoglobulin units. This is manifested as a broad energy minimum at the intermediate inter-molecular distance of the inter-protein free energy profiles; thereby, demonstrating the formation of a nano-scale flocculant, followed by a potential gel, composed of protein particles. Practically, this property could be exploited to entrap further bioactive components within the protein matrix for novel engineered food materials. Furthermore, it was found that the anti-bacterial peptide regions of apo-lactoferrin are unaffected by the acidic pH, indicating the potential capability of apo-lactoferrin to act against harmful bacteria. Overall, this work unveils an understanding at a molecular level regarding the structural changes of the aforementioned proteins that maybe beneficial for future advancement of nutraceuticals.

Evaluation of the bioaccessibility of tetrahydrocurcumin-hyaluronic acid conjugate using in vitro and ex vivo models

Tetrahydrocurcumin-hyaluronic acid (THC-HA) conjugate was synthesized in order to improve the bioaccessibility of tetrahydrocurcumin (THC). The successful conjugation was confirmed by the results from 1H-nuclear magnetic resonance (1H NMR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Bioaccessibility enhancement from the THC-HA conjugate compared to the free crystalline THC suspension was demonstrated by the results from ex vivo Franz diffusion cell using small intestine from porcine and in vitro TNO dynamic gastrointestinal model-1 (TIM-1). Additionally, in vitro release was studied, and the integrity of the conjugate in both simulated gastric and intestinal conditions was found to maintain for up to 4 h. Mucoadhesive assay and rheological results indicated that the mucoadhesive property of THC-HA, in combination with the aqueous solubility enhancement, might contribute to the increased bioaccessibility. This study provides a promising approach to enhance the bioaccessibility of tetrahydrocurcumin through the innovative conjugation with hyaluronic acid.

Development of Probiotic Lactobacillus sporogenes Loaded Biological Macromolecules using Novel Assembly Design for Long-term Preservation as Bio-therapeutic Agent

The goal present investigation was to formulate and characterized of biological macromolecules of alginate (ALG) and carboxymethylcellulose sodium (CMC) containing probiotic bacteria of Lactobacillus sporogenes (LS) co-encapsulated with a prebiotics, Bioecolians (α-Gluco-oligosaccharides). The prepared beads were characterized in terms of yield, size, encapsulation efficiency, viabilities in simulated gastric (pH 1.2, 2 hours) and bile (1% w/v, 3 hours) conditions. The beads were also characterized by FTIR, DSC, SEM and XRD to investigate molecular structure, surface properties and morphology of beads. The results showed that spherical beads with size distribution ranging from 1.18 ± 0.11 to 1.45 ± 0.15 mm for ALG and from 1.3 ± 0.12 to 1.5 ± 0.16 mm for ALG-CMC with encapsulation efficiency higher than 90% were achieved. The results indicated that incorporation of carboxymethylcellulose sodium into alginate beads improved viability of the bacteria in simulated gastric conditions as well as bile conditions. According to our in vitro studies, Probiotic beads using combination of ALG-CMC are suitable encapsulating polymer for gastro-intestinal delivery as designed by novel assembly using peristaltic pump for automated production.

MICROENCAPSULATION OF L. FERMENTUM ISOLATED FROM TRADITIONAL DAIRY PRODUCTS AND ITS STABILITY ON EXPOSURE TO SIMULATED GASTROINTESTINAL CONDITIONS

The physiological state of food may affect the survival potential of health promoting microorganisms. The current research was thus undertaken for comparing the invitro stability of two similar species of L. fermentum isolated from two different dairy products. The isolates were analyzed for their viability after microencapsulation in sodium alginate and were also compared using the non-encapsulated strain in simulated gastric and intestinal conditions. Viability of the cultures were also compared against reference standard (i.e) Lactobacillus acidophilus procured from MTCC Chandigarh. The percentage log reduction of non- encapsulated cultures i.e curd, raw milk and MTCC was 58.32%,58.28%,58.43% while that of encapsulated cultures was 10.19%, 10.03% and 11.18% as observed in gastric juice. The log reduction of non -encapsulated cultures as observed was 3.80%, 3.10% and 2.23% for curd raw milk and MTCC cultures respectively while that of encapsulated cultures was 1.54%, 1.52% and 1.16%in simulated intestinal conditions. The raw milk isolate was found with slightly better adaptation in response to the viability both in case of gastric and intestinal juice. The result thus justifies the physiological state of food which may affect the osmotic response and stress of similar microflora although isolated from two different food consortiums.

Utilization of sonication-glycation to improve the functional properties of ovalbumin: A high-resolution mass spectrometry study

Ovalbumin (OVA) is a globular protein found in hen's eggs that has excellent nutritional and functional properties but is a major allergen. Previous studies have shown that ultrasound pretreatment combined with glycation (sonication-glycation) of OVA markedly reduced its IgG and IgE binding capacities and enhanced its antioxidant activity. In this study, the effects of sonication-glycation on a number of important functional attributes of OVA were studied: foaming, emulsifying, and digestibility. These processes significantly enhanced the foaming and emulsifying properties of OVA by increasing the exposure of hydrophobic residues at the protein surfaces. Moreover, reversed-phase chromatography indicated that sonication-glycation only caused a small decrease in OVA digestibility under simulated gastric and small intestine conditions, and that the level of IgG and IgE binding of OVA was exceedingly low after digestion. Furthermore, sonication promoted the glycation of OVA by increasing the number of exposed glycation sites, as determined by high-resolution mass spectrometry. These results imply that sonication-glycation is a promising method for improving the functional performance of food proteins, while also reducing their immunogenicity.

Effect of Silk Fibroin Biomaterial Coating on Cell Viability and Intestinal Adhesion of Probiotic Bacteria.

Probiotics can be processed into a powder, tablet, or capsule form for easy intake. They are exposed to frequent stresses not only during complex processing steps, but also in the human body after intake. For this reason, various coating agents that promote probiotic bacterial stability in the intestinal environment have been developed. Silk fibroin (SF) is a material used in a variety of fields from drug delivery systems to enzyme immobilization and has potential as a coating agent for probiotics. In this study, we investigated this potential by coating probiotic strains with 0.1% or 1% water-soluble calcium (WSC), 1% SF, and 10% trehalose. Under simulated gastrointestinal conditions, cell viability, cell surface hydrophobicity, and cell adhesion to intestinal epithelial cells were then measured. The survival ratio after freeze-drying was highest upon addition of 0.1% WSC. The probiotic bacteria coated with SF showed improved survival by more than 10.0% under simulated gastric conditions and 4.8% under simulated intestinal conditions. Moreover, the cell adhesion to intestinal epithelial cells was elevated by 1.0-36.0%. Our results indicate that SF has positive effects on enhancing the survival and adhesion capacity of bacterial strains under environmental stresses, thus demonstrating its potential as a suitable coating agent to stabilize probiotics throughout processing, packaging, storage and consumption.

Tailoring the composition of hydrogel particles for the controlled delivery of phytopharmaceuticals

Understanding the factors that control biopolymeric carriers' drug release profiles is essential to determine their applicability as drug delivery systems. We attempted to evaluate the relationships between the kinetics of the release of selected phytopharmaceuticals from a series of polysaccharide-based particles and the physicochemical properties of the resulting macro- and microcarriers, including alginate (ALG)- and carboxymethyl cellulose (CMC)-based particles with gelatine (GEL) or chitosan (CHIT) shells. Hydrogel beads (612–1080 μm) and microparticles (8.5–44 μm) were successfully loaded with esculin (ESC), hesperidin (HES), or thyme oil (TO), their morphology was elucidated by scanning electron microscopy (SEM), and the encapsulation efficiency was determined by spectrophotometry. The hydrogel carriers exhibited a prolonged payload release (~90–300 min) under simulated gastrointestinal conditions, dependent on the coating type and pH environment. The variations in the particle composition influenced the drug release profiles, which were directly related to the carrier composition and payload characteristics. The Korsmeyer-Peppas and Peppas-Sahlin models, as well as a newly proposed hybrid model, provided the most appropriate description of the payload release from our particles when considered separately under the simulated gastric and intestinal conditions. Additionally, the Gallagher-Corrigan model was selected as the adequate one for predicting the consecutive payload release under those conditions. Establishing the most desirable mathematical model to predict the release profiles facilitated our comprehensively study the mechanism and release kinetics from multiple types of polysaccharide-based delivery vehicles loaded with phytopharmaceuticals possessing different structural and chemical features (i.e., water solubility and log P).

Simulated gastric hydrolysis and developmental toxicity of dibutyltin bis(2-ethylhexyl thioglycolate) in rats.

Previously, dibutyltin dichloride (DBTC) was the putative toxophore for dibutyltin bis-alkyl and bis-thio esters. Recent chemical and toxicological data on dioctyltin bis(2-ethylhexyl thioglycolate) suggest the thioglycolate esters of alkyltins do not generate the dichloride toxophore. Our results, using 119 Sn-nuclear magnetic resonance (NMR) spectroscopy, demonstrated that dibutyltin bis(2-ethylhexyl thioglycolate) (DBTE) is hydrolyzed to dibutyltin chloro-(2-ethylhexyl thioglycolate) (DBTEC) under simulated gastric conditions. No DBTC was detected. DBTE was administered orally to presumed-pregnant Sprague-Dawley rats in a corn oil vehicle at 2.5, 8.5, and 25.0 mg/kg/day (Gestation Day 5 [GD5] through GD19). There were no maternal deaths, no treatment-related statistically significant reductions in feed consumption, maternal body weight or weight gain, or adverse gestational outcomes. Maternal thymus weight was significantly reduced in rats at 25 mg/kg. There were no effects on fetal growth, no dose-dependent pattern of external, visceral, or skeletal malformations, and no increase in anatomical variations. Based on the obtained experimental data, it is concluded here that DBTE forms DBTEC, not DBTC, in the stomach, and DBTE was not teratogenic nor fetotoxic in rats, a species sensitive to DBTC. The maternal no-observed-adverse-effect level (NOAEL) was 8.5 mg/kg/day, and the developmental NOAEL was 25 mg/kg/day, the high dose. The maternal LOAEL was 25 mg/kg/day based on reduced maternal thymus weight.