Simulated Gastric Environment Research Articles

Insulin Conformation Changes in Hybrid Alginate-Gelatin Hydrogel Particles.

There is a strong need to develop an insulin delivery system suitable for oral administration and preserving natural (α-helix) insulin conformation. In this work, we fabricated alginate-gelatin hydrogel beads for insulin encapsulation. Altering matrix composition and crosslinking agents has resulted in various surface morphologies and internal spatial organization. The structures of the insulin-loaded matrices were studied using optical and field emission electronic microscopy. We use FTIR spectroscopy to identify insulin conformation changes as affected by the hydrogel matrices. It was found that blended alginate-gelatin matrices demonstrate better encapsulation efficiency and stronger swelling resistance to a simulated gastric environment than sodium alginate beads crosslinked with the CaCl2. FTIR measurements reveal conformation changes in insulin. It is also confirmed that in the presence of gelatin, the process of insulin fibrinogenesis ceases due to intermolecular interaction with the gelatin. Performed molecular modeling shows that dipole-dipole interactions are the dominating mechanism that determines insulin behavior within the fabricated matrix.

Investigating the stability of vitamin D3 and Bifidobacterium lactis nanoparticles coated with polycaprolactone-polyethylene glycol-polycaprolactone triblock copolymer in Iranian white cheese and determining its physicochemical and sensory properties

ObjectiveTo investigate the stability and efficacy of vitamin D3 and Bifidobacterium lactis nanoparticles coated with polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) in enhancing the nutritional value of Iranian white cheese and to assess their impact on the cheese's physicochemical and sensory properties. MethodsBifidobacterium lactis and vitamin D3 were encapsulated using PCL-PEG-PCL. The particle size was analyzed using Dynamic Light Scattering (DLS). Five different cheese groups were produced and analyzed over two months. This included assessing microbial viability in simulated gastric and intestinal environments, quantifying vitamin D3 content, and evaluating physicochemical and sensory characteristics using a 9-point hedonic scale. ResultsThe Cheese with Bifidobacterium lactis coated with PCL-PEG-PCL and vitamin D3 nanoparticles (BCND3), showed a marked improvement in the stability of both Bifidobacterium lactis and vitamin D3. Specifically, the coated bacteria maintained a concentration of 106 cfu/g until day 45 in the intestinal model, demonstrating effective protection against the acidic gastric environment. The vitamin D3 nanoparticles displayed enhanced stability within the cheese matrix, contributing to the nutritional value and potentially extending the shelf life. Physicochemically, initial pH reduction due to lactic acid production stabilized by day 60, aligning with other groups. Sensory evaluation revealed a preference for the softer texture of cheese with vitamin D3 nanoparticles, suggesting a positive impact on consumer acceptability. ConclusionThe application of PCL-PEG-PCL coating significantly improved the stability of probiotics and vitamin D3 in cheese. This method proved effective in protecting Bifidobacterium lactis from harsh gastrointestinal conditions and in sustaining vitamin D3 content, with a notable impact on the cheese's sensory qualities. These findings highlight the potential of this coating technique in food fortification strategies.

Investigating the prilling/vibration technique to produce gastric-directed drug delivery systems for misoprostol

Prilling/vibration technique to produce oral microcapsules was explored to achieve local delivery of misoprostol (MIS), a prostaglandin E1 analogue indicated for the treatment of gastric-duodenal ulcers, at the gastric mucosa. To improve MIS chemical stability and reduce its associated systemic side effects, drug delivery systems were designed and developed as microcapsules consisting of a core of sunflower oil and MIS (Fs6 and Fs14) or a MIS complex with hydroxypropyl-beta-cyclodextrin (HP-β-CD) (Fs18), confirmed by specific studies, and a polymeric shell. The produced microcapsules showed high encapsulation efficiencies for those with MIS solubilized in sunflower oil (>59.86 %) and for the microcapsules with MIS/HP-β-CD (97.61 %). To demonstrate the ability of these systems to deliver MIS into the stomach, swelling and drug release experiments were also conducted in simulated gastric fluid. Among the three formulations, FS18 showed gastric release within 30 min and was the most advantageous formulation because the presence of the MIS/HP-β-CD inclusion complex ensured a greater ability to stabilise MIS in the simulated gastric environment. In addition, these new systems have a small size (<540 µm), and good flow properties and the dose of the drug could be easily adapted using different amounts of microcapsules (flexibility), making them a passepartout for different age population groups.

In vitro digestion under simulated saliva, gastric and small intestinal conditions and fermentation of nicotinamide mononucleotide, and its effects on the gut microbiota

Nicotinamide Mononucleotide (NMN) is a derivative of vitamin B3, which plays a significant role in a plethora of metabolic reactions in the human body and is intricately associated with both immunity and metabolism. Nonetheless, in the intestine metabolic pathway of NMN and the relationship between NMN, gut microbiota, and SCFAs remain hitherto obscure. This study examined the digestion of NMN in simulated saliva, gastric, and small intestine environments, as well as exploring the interaction between NMN and human gut microbiota utilizing an in vitro fermentation model. NMN was progressively degraded into nicotinamide ribose (NR), nicotinamide (NAM), and ribose, with niacinate (NA) constituting the ultimate degradation product due to hydrolysis and metabolism by microbiota. NMN was ingested by human intestinal microbiota with a slower fermentation rate. As a result of NMN ingestion by human gut bacteria，the concentrations of propionate and butyrate increased by 88% and 23%, respectively, compared to the blank control group, the proliferation of beneficial gut bacteria (Bifidobacterium, Phascolarctobacterium, Faecalibacteriun, and Alistipes) significantly increased, while the proliferation of some harmful bacteria (Sutterella, Desulfovibrio and Pseudomonas) drastically declined. These findings illustrated the metabolic processes of NMN in the intestine, elaborating the relationship between NMN, SCFAs and gut microbiota. NMN might be a potential prebiotic to improve intestinal health.

247 In Vitro Characterization of Equine Fore- and Midgut Digestion

Abstract Considerable advancements can be made in the field of equine nutrition and diet formulation, by improved feed characterization and the development of nutritional models, including in vitro models, to describe nutrient degradation. Methodologically, literature values for in vitro small intestine incubation times are widely variable ranging from 2 to 18 h. While some incubation times are selected to represent approximate mean retention times, conversely, insufficient in vitro incubation times and sampling time points could prohibit or result in inaccuracies characterizing nutrient degradability characteristics, ultimately affecting both degradability and digestion values and their use. The objective of this trial was to assess whether macronutrient degradability plateaus when digested for 2 h in a simulated gastric environment plus 8, 12, or 16 h in a simulated small intestinal environment. To replicate in vivo digestion, a pepsin-pancreatin approach was selected. The first step of this method replicates the gastric environment. Ten g of each test ingredient are weighed into beakers containing 60 mL hydrochloric acid (HCl; 0.1 M) and 0.4 g pepsin (~2,500 U/g) solution. Beakers are then covered and incubated for 2 h at 39 ℃ under constant stirring. One mL aliquots of the digestion liquid are sampled at 0, 5, 10, 20, 30 60, 90 and 120 min after the start of the gastric simulation. Before replicating intestinal digestion, samples are neutralized with sodium hydroxide and the pH is increased to 7. The second step of this method replicates the small intestinal environment. Fifty mL of pancreatin-phosphate buffer (350 U/g protease, 6,000 FIP U/g lipase, 7,500 U/g amylase) is added to the beakers, which are then covered and incubated for either 8, 12, or 16 h at 39 ℃ under constant stirring. One mL aliquots of the digestion liquid are sampled at 0, 5, 10, 20, 30 60, 90, 120, 150, 180 min and thereafter hourly up until the end of digestion (480, 720, or 960 min). Aliquot samples are analyzed for starch via a glucose assay, protein via o-phthalaldehyde assay, and lipids via gas chromatography. A model will is fit to the time point data to determine degradation rates and degradable fractions of the digested samples. Results from these analyses go beyond estimating gross nutrient and digestible nutrient values and inform on the rate of degradation of nutrients of equine feedstuffs and the impact of in vitro methodology. The resulting degradability values will be used in a mechanistic model of equine digestion which will inform precision feeding. Ultimately this will improve how we feed horses to reduce nutrient excretion into the environment and reduce the risk of metabolic conditions such as laminitis.

Improvement of solubility of epimedium flavonoid secondary glycoside components by traditional Chinese medicine polysaccharides and its mechanism

The poor solubility of insoluble components of traditional Chinese medicine(TCM) is an important factor restricting the development of its preparations. Natural polysaccharides of TCM can be used as functional components to increase the solubility of insoluble components. Epimedium flavonoid secondary glycoside components(EFSGC) have been shown to have positive effects on the prevention and treatment of osteoporosis, but they exhibit poor solubility. Therefore, the strategy of solubilizing EFSGC with TCM polysaccharides was adopted, and its effect on the permeability and stability of EFSGC was evaluated in this study. Based on the equilibrium solubility experiment of EFSGC, it was found that Panax notoginseng crude polysaccharide(PNCP) had the best solubilization effect on EFSGC among the ten kinds of TCM polysaccharides, which increased the solubility of EFSGC from 0.8 mg·mL~(-1) to 13.3 mg·mL~(-1). It should be noted that after the solubilization of EFSGC by preparation technology, the effects on permeability and stability should be considered. Therefore, this study also investigated these two properties. The results showed that PNCP increased the effective transmittance of EFSGC from 50.5% to 71.1%, which could increase the permeability of EFSGC significantly. At the same time, it could improve the stability of EFSGC in the simulated gastric juice environment. In order to explain the solubilization mechanism of PNCP on EGSGC, critical micelle concentration, particle size, potential, differential scanning calorimetry, and infrared spectroscopy were analyzed. It was preliminarily inferred that the mechanism was as follows: PNCP and EFSGC could self-assemble into aggregates for solubilization by intermolecular hydrogen bonding interaction in water. In summary, PNCP can not only improve the solubility of EFSGC but also improve its permeability and stability. This study lays the foundation for the application of TCM polysaccharides as a functional component to solubilize insoluble components.

PH-Responsive Polymeric Micelle Dynamic Complexes for Selective Killing of Helicobacter pylori.

Helicobacter pylori, the world's most common chronic infection-causing pathogen, is responsible for causing gastric ulcers, the fourth-leading cause of cancer-related death globally in 2020. In recent years, the effectiveness of the current treatment regimen (two antibiotics and one proton pump inhibitor) has often been plagued with problems such as resistance and the undesired elimination of commensal bacteria. Herein, we report the synthesis of block and random copolycarbonates, functionalized with cationic guanidinium and anionic acetate functional groups, aimed at selectively killing H. pylori in the acidic environment of the stomach, while remaining nontoxic to the commensal bacteria in the gut. The compositions of the polymers were fine-tuned so that the polymers were readily dispersed in water without any difficulty at both pH 3.0 and 7.4. The self-assembly behavior of the polymers at different pH values by dynamic light scattering showed that the random and block copolymers formed stable micelles in a simulated gastric environment (pH 3.0) while aggregated at pH 7.4. Both polymers demonstrated stronger antibacterial activity against H. pylori than the guanidinium-functionalized homopolymer without any acetate functional group at pH 3.0. The block copolymer was significantly more bactericidal at pH 3.0 across the concentrations tested, as compared to the random copolymer, while it did not show significant toxicity toward rat red blood cells (rRBCs) and HK-2 cells or bactericidal effect toward E. coli (a common gut bacterium) and nor caused aggregation of rRBCs at its effective concentration and at physiological pH of 7.4. Additionally, both the block and random copolymers were much more stable against hydrolysis at pH 3.0 than at pH 7.4. This study provides insight into the influence of both polymer architecture and dynamic assembly on the bioactivities of antimicrobial polymers, where the disassembly of coacervates into narrowly dispersed micelles at pH 3 make them potent antimicrobials aided by the protonated carboxylic acid block.

Nanoencapsulation of α-mangostin using chitosan-oleic acid complexes: Evaluation of storage stability, in vitro release properties in simulated digestive environment, and bioaccessibility

The mangosteen fruit possesses a potent antioxidant known as α-mangostin. However, the poor aqueous solubility of α-mangostin limits its incorporation into food products, as well as its oral bioaccessibility in the human gastrointestinal tract. Therefore, we utilized electrostatic complexation between chitosan and oleic acid to encapsulate α-mangostin as a strategy to overcome these limitations. As a result, a homogeneous nanoparticle suspension (average particle diameter = 830 nm) was achieved, as verified by scanning transmission electron microscopy and laser diffraction particle size analysis. Importantly, the aqueous solubility of α-mangostin was significantly improved (>800 times), as examined using high-performance liquid chromatography, enabling its effective incorporation into foods and beverages. The nanoparticles were stable and conveniently stored in a dark vial at 4 °C for more than 2 weeks. In the simulated gastric environment, the pH sensitivity of the chitosan-oleic acid complexes enabled the α-mangostin to remain encapsulated in the gastric phase (pH 3) and to be released in the intestinal phase (pH 7) with a bioaccessibility percentage greater than 50%. Overall, the novel synthesized α-mangostin-encapsulated nanoparticles are beneficial for the design of functional foods with enhanced quality, gastrointestinal stability, and delivery.

Encapsulated fucoxanthin improves the structure and functional properties of fermented yogurt during cold storage.

Fucoxanthin (FX) extracted from Undaria pinnatifida by an ultrasonic-assisted extraction (UAE) procedure was successfully added to the fermented yogurt through a stably nanoencapsulation. The physicochemical characteristics, texture analysis, rheological testing, sensory evaluation, simulated digestion analysis, and 16SrDNA sequencing analysis were used to evaluate the effect of encapsulated-FX on the function, structure and stability of the fermented yogurt during 7days cold storage. Encapsulated-FX with a highly water dispersion, changed the microstructure of yogurt, making it more uniform and denser, enhanced the antioxidant activity, increased the stability of milk protein in simulated gastric environment in vitro and promoted the absorption of protein small molecule fragments in the intestine, and inhibited the growth of harmful bacteria during cold storage. This study provided a simple strategy for the production of FX-fortified yogurt by using an effective nanoencapsulation technology, and promoted the extraction and application of active ingredients of edible brown algae.

Small polystyrene microplastics interfere with the breakdown of milk proteins during static in vitro simulated human gastric digestion

Human ingestion of microplastics (MPs) is common and inevitable due to the widespread contamination of food items, but implications on the gastric digestion of food proteins are still unknown. In this study, the interactions between pepsin and polystyrene (PS) MPs were evaluated by investigating enzyme activity and conformation in a simulated human gastric environment in the presence or absence of PS MPs. The impact on food digestion was also assessed by monitoring the kinetics of protein hydrolysis through static in vitro gastric digestion of cow's milk contaminated with PS. The binding of pepsin to PS showed that the surface chemistry of MPs dictates binding affinity. The key contributor to pepsin adsorption seems to be π−π interactions between the aromatic residues and the PS phenyl rings. During quick exposure (10 min) of pepsin to increasing concentrations (222, 2219, 22188 particles/mL) of 10 μm PS (PS10) and 100 μm PS (PS100), total enzymatic activities were not affected remarkably. However, upon prolonged exposure at 1 and 2 h, preferential binding of pepsin to the small, low zeta-potential PS caused structural changes in the protein which led to a significant reduction of its activity. Digestion of cow's milk mixed with PS10 resulted in transient accumulation of larger peptides (10–35 kDa) and reduced bioavailability of short peptides (2–9 kDa) in the gastric phase. This, however, was only observed at extremely high PS10 concentration (0.3 mg/mL or 5.46E+05 particles/mL). The digestion of milk peptides, bound preferentially over pepsin within the hard corona on the PS10 surface, was delayed up to 15 min in comparison to bulk protein digestion. Intact caseins, otherwise rapidly digested, remained bound to PS10 in the hard corona for up to 15 min. This work presents valuable insights regarding the interaction of MPs, food proteins, and pepsin, and their dynamics during gastric digestion.

Design of SC PEP with enhanced stability against pepsin digestion and increased activity by machine learning and structural parameters modeling

Prolyl endopeptidases from Sphingomonas capsulata (SC PEP) has attracted much attention as promising oral therapy candidate for celiac sprue, however, its low stability in the gastric environment leads to unsatisfactory clinical results. Therefore, improving its stability against pepsin digestion at low pH is crucial for clinical applications, but challenging. In this study, machine learning and physical parameter model were combined to design SC PEP mutants. After iterations, 20 mutants had higher hydrolysis activity in stomach environment, which was up to 14.1-fold compared with wild-type SC PEP. Mutant M24 involving stable and active mutations and pegylated M24 (M24-PEG) had higher activity of hydrolyzing immunogen in bread than wild-type SC PEP in vitro and in vivo, and residual immunogens in simulated gastric environment were only 1/8 and 1/10 of that in the wild-type SC PEP group. The total residual immunogens in the gastrointestinal tract of mice in the M24 and M24-PEG groups were <20 ppm, reaching the standard of non-toxic food. Our results indicate that the combination of M24 (or M24-PEG) with EP-B2 may be a promising candidate for celiac disease, and the strategies developed in this study provide a paradigm for the design of SC PEP stability mutants.

In vitro dissolution/permeation tools for amorphous solid dispersions bioavailability forecasting II: Comparison and mechanistic insights

Along with the increasing demand for complex formulations comes the need for appropriate in vitro methodologies capable of predicting their corresponding in vivo performance and the mechanisms controlling the drug release which can impact on in vivo drug absorption. In vitro dissolution-permeation (D/P) methodologies that can account for the effects of enabling formulations on the permeability of drugs are increasingly being used in performance ranking during early development stages. This work comprised the application of two different cell-free in vitro D/P setups: BioFLUX™ and PermeaLoop™ to evaluate the dissolution-permeation interplay upon drug release from itraconazole (ITZ)- HPMCAS amorphous solid dispersions (ASDs) of different drug loads. A solvent-shift approach was employed, from a simulated gastric environment to a simulated intestinal environment in the donor compartment. PermeaLoop™ was then combined with microdialysis sampling to separate the dissolved (free) drug from other species present in solution, like micelle-bound drug and drug-rich colloids, in real time. This setup was applied to clarify the mechanisms for drug release and permeation from these ASDs. In parallel, a pharmacokinetic study (dog model) was conducted to assess the drug absorption from these ASDs and to compare the in vivo results with the data obtained from each in vitro D/P setup, allowing to infer which would be the most adequate setup for ASD ranking. Even though both D/P systems resulted in the same qualitative ranking, BioFLUX™ overpredicted the difference between the in vivo AUC of two ASDs, whereas PermeaLoop™ permeation flux resulted in a good correlation with the AUC observed in pharmacokinetic studies (dog model) (R2 ≈ 0.98). Also, PermeaLoop™ combined with a microdialysis sampling probe clarified the mechanisms for drug release and permeation from these ASDs. It demonstrated that the free drug was the only driving force for permeation, while the drug-rich colloids kept permeation active for longer periods by acting as drug reservoirs and maintaining constant high levels of free drug in solution, which are then immediately able to permeate. Hence, the data obtained points BioFLUX™ and PermeaLoop™ applications to different momentums in the drug product development pipeline: while BioFLUX™, an automated standardized method, poses as a valuable tool for initial ASD ranking during the early development stages, PermeaLoop™ combined with microdialysis sampling allows to gain mechanistic understanding of the dissolution-permeation interplay, being crucial to fine tune and identify leading ASD candidates prior to in vivo testing.

Stability Characterization of the Novel Anti-Cancer HM-10/10 HDL-Mimetic Peptide.

Epithelial adenocarcinoma of the ovary and colon are associated with the highest rates of cancer-related deaths in women in the U.S. The literature supports the role of HDL-associated apolipoproteins in the treatment of cancer and other pro-inflammatory diseases. Previously, we developed a novel 20-amino acid mimetic peptide, HM-10/10, which potently inhibits tumor development and growth in colon and ovarian cancer. Here, we report the properties of HM-10/10 relative to its stability in vitro. The results demonstrated that HM-10/10 had the highest half-life in human plasma compared to plasma from other species tested. HM-10/10 demonstrated stability in human plasma and simulated gastric environment, increasing its promise as an oral pharmaceutical. However, under conditions modeling the small intestine, HM-10/10 demonstrated significant degradation, likely due to the peptidases encountered therein. Furthermore, HM-10/10 demonstrated no evidence of time-dependent drug-drug interactions, although it demonstrated CYP450 induction slightly above cutoff. As proteolytic degradation is a common limitation of peptide-based therapeutics, we are pursuing strategies to improve the stability properties of HM-10/10 by extending its bioavailability while retaining its low toxicity profile. HM-10/10 holds promise as a new agent to address the international women's health crisis of epithelial carcinomas of the ovary and colon.

Evaluation of the probiotic potential of Enterococcus faecium NCIMB 11181 as a possible candidate in animal nutrition

Abstract Enterococcus faecium (NCIMB 11181) was evaluated for survivability, safety, and capacity as probiotics utilization. Gram-positive, catalase-negative test, antibiotics susceptibility, hemolysis activity, pH and bile salts resistance were screened using selective microbiological media. The strain was phenotypically assessed for its principal probiotic properties. The capacity of fermentation based on biochemical tests was evaluated by API 20STREP and interpretation by apiwebTM Biomerieux (France) software (99.2% very good identification). After incubation at 37°C for 22-24 h in aerobic conditions, E. faecium involves 13.96 Log10 with an optical density (OD 600 nm) from 0.2 in the first 2 hours of growth to 0.9 value. The safety assessment on TSA agar showed that the strain revealed α-hemolysis. Resistance to 16 clinically relevant antibiotics, presented for our strain a range from intermediate (81.25%) to susceptible (6.25%), followed by resistance to erythromycin and colistin sulfate. The strain exhibited tolerance to acidic conditions and simulated gastric environment. Therefore, E. faecium NCIMB 11181 can be considered a safe strain without creating a risk to animal health status. It may be used as a probiotic preparation product for application in animal nutrition.

Total and bio-accessible toxic metals in low-cost children toys sold in major markets in Ibadan, South West Nigeria

Toxic metals are usually added to children's toys to improve/impact some intrinsic properties such as colour which attracts children. Some of the toxic metals have life-threatening potentials on children when ingested. There is no specific legislation in Nigeria that monitors and regulates limits of such metals in toys. This study assessed total and bio-accessible concentrations of Pb, Cd, Cr, Ni, and Mn in imported low-cost children's plastic toys sold in popular markets in Ibadan, Nigeria. A total of 22 different toys were purchased and subjected to an indicative test for the presence of polyvinyl chloride (PVC) following the Beilstein method as well as analysing for total recoverable metals and migrated fractions into simulated saliva and gastric environments. Toy samples were crushed, ashed, and dissolved with dilute nitric acid for total recoverable metals while migration studies were carried out using simulated saliva and gastric environments to check bio-accessible fractions that could leach into the human system. Metals in all extracts were determined using flame atomic absorption spectrophotometric technique. The indicative PVC test showed 12 samples positive to PVC and 10 tested negative. Total recoverable metal concentrations (mg/kg) ranged as follows: Pb: Below Detection Limit (BDL) - 4838, Cd: BDL - 44.9, Cr: 0.331–79.8, Ni: 0.273–59.1 and Mn: 0.205–31.0 with Pb and Cr having 18 and 14% of samples higher than EU limits of 90 and 60 mg/kg. Bio-accessible concentrations in artificial saliva were: Pb: BDL - 42.4, Cd: BDL-0.450, Ni: BDL-1.40 and Mn: BDL-0.058 with Pb higher in 70% of samples compared to 2.0 mg/kg migrated EU limit while other metals were within the limits. Furthermore, metal concentrations that migrated to gastric environment were: Pb: 8.24–50.3, Cd: BDL-0.057, Ni: 0.103–1.96 and Mn: BDL-1.37 with Pb in 100% of samples higher than 2.0 mg/kg EU migrated limit. Chromium migration in both environments was BDL. The results of this study suggest that toxic metal contents are present in both PVC and non-PVC made toys, but higher in PVC containing toys. Though the calculated hazard index for health risk assessment of heavy metals was < 1 for all metals, Pb concentration in both total recoverable extract and saliva and gastric environments seem to be problematic and constant monitoring and regulation are required.

Encapsulation in Amylose Inclusion Complex Enhances the Stability and Release of Vitamin D.

Vitamin D plays a significant role in the physiological functions of the human body. However, the application of vitamin D in functional foods is limited due to its sensitivity to light and oxygen. Therefore, in this study, we developed an effective method to protect vitamin D by encapsulating it in amylose. In detail, vitamin D was encapsulated by amylose inclusion complex, followed by structural characterization and evaluation of its stability and release properties. The results of X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy showed that vitamin D was successfully encapsulated in the amylose inclusion complex, and the loading capacity was 1.96% ± 0.02%. The photostability and thermal stability of vitamin D after encapsulation was increased by 59% and 28%, respectively. In addition, in vitro simulated digestion showed that vitamin D was protected through the simulated gastric environment and can be released gradually in the simulated intestinal fluid, implying its improved bioaccessibility. Our findings provide a practical strategy for the development of functional foods based on vitamin D.

Characterization and evaluation of an oral vaccine via nano-carrier for surface immunogenic protein (Sip) delivery against Streptococcus agalactiae infection

Streptococcus agalactiae causes systemic disease in a variety of wild and farmed fish, resulting in high levels of morbidity and mortality, as well as serious economic losses to the Nile tilapia aquaculture industry. The development of economic and applicable oral vaccines is therefore urgently needed for the sustainable development of Nile tilapia aquaculture. In this study, mesoporous silica nanoparticles (MSNs) were fabricated using sol–gel synthesis technology, and the antigens of surface immunogenic protein (Sip) was loaded into MSNs to develop a nanovaccine MSNs-Sip@HP55. The results showed that the prepared nanovaccine exhibited pH-controlled release, which could survive in the simulated gastric environment (pH 1.5), and release antigens in the simulated intestinal environment at pH 7.4. The nanovaccine could induce innate and adaptive immune responses in Nile tilapia. When the challenge doses were 1.5 × 106, 1.18 × 106, and 0.88 × 106 CFU/mL, the relative protection rates in immunized Nile tilapia were 63.33 %, 64.23 %, and 76.31 %, respectively. Taken together, the nanovaccine exhibited a high antigen utilization rate and was easily administered orally via feeding, which could protect Nile tilapia against challenge with S. agalactiae in large-scale farms. Oral vaccine based on MSNs carriers is a potentially promising strategy for the development of fish vaccines.

Conformational evolution of soybean protein-polysaccharide at oil–water interface in simulated gastric environment in vitro

The conformation and characteristics of soybean hull polysaccharide (SHP)/soy bean protein isolate (SPI) complex at oil–water interface in simulated gastric environment in vitro were discussed. Isothermal titration calorimetry (ITC) thermodynamic results illustrated that SPI formed a complex with SHP. ζ-potential and microstructure showed a flocculation phenomenon after SPI/SHP emulsion droplet treatment (especially at 60 min), which indicated that the inter droplet steric hindrance and repulsion were reduced after the emulsion was treated. Additionally, at 60 min, in FT-IR spectrum fitting results, the contents of β-sheet and β-turn structure were the lowest, which might be that the polar group residues exposed in the SPI/SHP complex at the interface interacted with Na+ by ion–dipole interaction or protonated with H+. The blue shift of maximum absorption intensity also indicated that the tryptophan residues moved to the hydrophobic environment, which made the treated droplets flocculate without obvious aggregation.

Composition-Property Relationships of pH-Responsive Poly[(2-vinylpyridine)-co-(butyl methacrylate)] Copolymers for Reverse Enteric Coatings.

The taste-masking of bitter-tasting active pharmaceutical ingredients is key to ensuring patient compliance when producing oral pharmaceutical formulations. This is generally achieved via the incorporation of pH-responsive, reverse enteric polymers, that prevent the dissolution of the formulation in the oral environment, but rapidly mediate it within the gastric environment. Reverse enteric polymers are commonly applied as coatings on oral dosage forms via spray atomisation (e.g., fluidised-bed spray coating), and generally exhibit the most efficient taste-masking. However, currently used reverse enteric coatings require high mass gains (% w/w) during coating to mediate taste-masking, and thereby exhibit delayed release within the gastric environment. Therefore, there remains a need for the development of new reverse enteric coatings, that can efficiently taste-mask at low mass gains and maintain rapid release characteristics within the gastric environment. Herein we report the synthesis and evaluation of a series of addition copolymers of 2-vinylpyridine and butyl methacrylate, methyl methacrylate and isobornyl methacrylate. The thermal, solubility, and water absorption properties of the copolymers were effectively tuned by altering the mol% fraction of the constitutive monomers. Based on their physical properties, selected copolymers were preliminarily evaluated for their compatibility with fluidised-bed spray coating, and effectiveness as taste-masking reverse enteric coatings. The copolymers poly[(2-vinylpyridine)-co-(butyl methacrylate)] (mol% ratio 40:60) and poly[(2-vinylpyridine)-co-(butyl methacrylate)-co-(methyl methacrylate)] (mol% ratio 40:50:10) were found to exhibit excellent taste-masking properties following fluidised-bed spray coating onto Suglets® sugar spheres. Suglets® bearing a film coating of either copolymer (5.2-6.5% w/w mass gain) were found to effectively impede the release of a model drug formulation for up to 72 h in a simulated salivary environment, and rapidly release it (<10 min) within a simulated gastric environment. The results demonstrated the potential of poly[(2-vinylpyridine)-co-(butyl methacrylate)] copolymers to form effectively taste-masked, reverse enteric dosage forms, and suggested that these copolymers may provide improved performance compared to currently available polymers.

Chiral pharmaceutical drug adsorption to natural and synthetic particulates in water and their desorption in simulated gastric fluid

Natural and synthetic particulates in aquatic environments can act as a vector for chiral pharmaceutical drugs. Understanding enantiomer enrichment in the particulate phase of water matrices is essential considering the enantiospecific effects that chiral drugs can have on exposed organisms. Therefore, the enantiospecific adsorption of the cationic drugs fluoxetine and propranolol to polyhydroxyalkanoate bioplastic, polyamide microplastic, and cellulose particulates was investigated in 0.01 M calcium chloride (CaCl2) buffer and real environmental matrices. Fluoxetine enantiomers adsorbed to all particulate types under all conditions studied. Yet, propranolol only adsorbed to polyamide in 0.01 M CaCl2 buffer at pH 11, and in samples prepared using real matrices (river water and wastewater). No enantioselectivity was observed in the adsorption of fluoxetine or propranolol, or their subsequent desorption in a simulated gastric environment. Findings showed the enantiomeric composition of the adsorbed drug will reflect that of the dissolved drug assuming no degradation takes place. However, further enantiospecific adsorption studies are now needed on a broader range of chiral drugs and particulate matter found in water. Importantly, drug adsorption was considerably greater in river water and wastewater compared to 0.01 M CaCl2 buffer (2.1 to 5.3 times for fluoxetine). Most adsorption studies reported in the literature use 0.01 M CaCl2 buffer to conform with international guidelines for assessing the adsorption behaviour of chemicals. Although such conditions enable direct comparison with similar studies, they can underestimate cationic drug adsorption to particulates in engineered and natural environments. This needs consideration in future studies on drug adsorption to microplastics and other particulate matter in laboratory studies.