Stomach pH Research Articles

Exploration of thiazine Schiff bases as promising urease inhibitors: Design, synthesis, enzyme inhibition, kinetic analysis, ADME/T evaluation, and molecular docking studies

Urease catalyzes the hydrolysis of urea, leading to an increase in stomach pH and supporting Helicobacter pylori survival, which is linked to several gastrointestinal disorders. In this study, thiazine-based Schiff bases were explored as promising urease inhibitors. Various spectroscopic techniques characterized the synthetic library of thiazine Schiff bases 2–36 and also evaluated for their inhibitory activities against urease. The derivatives demonstrated significant inhibitory potential with IC50 values ranging from 0.14 ± 0.08 to 3.66 ± 0.21 μM, outperforming the standard inhibitor thiourea (IC50 = 19.43 ± 0.18 μM). Structure-activity relationship (SAR) studies revealed that specific substitutions (type and positions) on the aryl ring significantly affect the inhibition potential. The most potent derivative, compound 7, possessed 2-methoxy-5-trifluoromethyl substitutions and exhibited an IC50 of 0.14 ± 0.08 μM. Enzyme kinetics studies revealed that the most potent derivatives function as competitive inhibitors. Additionally, molecular docking studies provided insights into the binding interactions between the molecule and the urease active site, highlighting key residues involved in inhibitor binding. These findings highlight the therapeutic potential of thiazine-based Schiff bases as urease inhibitors and provide insights for the development of new anti-ulcer agents.

244 Comparative crude protein solubilization in yellow pea and fava bean protein concentrates in a simulated porcine gastric and intestinal digestion model

Abstract Pulses are valuable protein ingredients but unique characteristics among them are known to influence protein quality and utilization. We determined crude protein solubilization (CPS) in yellow pea (YP) and fava bean (FB) protein concentrates using simulated porcine gastric and intestinal model (Table 1). For each ingredient, 500 mg CP equivalent was incubated in triplicate with pepsin at either pH 3.5 or 4.5 for 0, 0.5, 1, and 1.5 h at 39°C and 200 r.p.m. for gastric CPS. For intestinal CPS, gastric samples (derived at pH 3.5 for 1.5 h) were incubated with pancreatin and bile extract at pH 6.8 for 0, 0.5, 2, 4 and 6 h. Intestinal CPS was categorized as CPfast, CPslow and CPresistant corresponding to CPS within the first 0.5 h, 0.5 to 4 h, and undigested after 4 h, respectively (Table 2). The concentration of CP in the supernatant was equated to CPS. Data were subjected to Proc GLIMIXX of SAS while Gompertz equation was used to describe the gastric and intestinal solubilization kinetics (A-maximum solubilized CP, Wo- initial CP solubility, Ku- solubilization rate, Ti- time to inflection). The model for gastric CPS had fixed effects of protein, incubation time, stomach pH and their interaction at 1.5 h and while fixed effects of protein was evaluated in intestinal CPS kinetics. The analyzed CP in FB and YP were 712.7 and 599.1, g/kg DM, with 3 and 4% of CP bound to NDF, respectively. Gastric CPS in FB was not influenced (P > 0.05) by pH and incubation time; however, at 1.5 h gastric CPS in FB was 40.9 and 28.44% at pH 3.5 and 4.5, respectively. Gastric CPS in YP was influenced by incubation time (P < 0.05) with increase at pH 3.5 after 1 h and at pH 4.5 after 0.5 h compared with 0 h. After 1.5 h, gastric CPS in YP was 50.0% at pH 3.5 and 33.2% at pH 4.5. Whereas YP gastric CPS at pH 3.5 and 1.5h was greater compared with FB, there were no differences (P > 0.05) between the FB and TP at pH 4.5. However, intestinal CPS tended (P < 0.10) to be greater for FB (91.7%) compared with YP (89.4%). The FP was solubilized faster (Ku; P < 0.05) than YP, supported by a (P < 0.05) higher CPfast of FB (87.8%) compared with YP (75.9%). CPresistent was found to be greater (P < 0.05) for YP (12.0%) than for FB (6.6%; Figure 1). In conclusion, fava, and pea protein concentrates had gastric protein solubilization that was dependent on pH. The less resistant protein in FB suggested a greater nutritive value than YP. Further research should determine ileal amino acids digestibility and the impact of incorporation in practical diets to characterize animal performance, health, and environment impact.

491 Processing and stomach pH influenced in vitro gastric protein solubilization kinetics in sunflower meal

Abstract The study aimed to evaluate the effect of processing and pH on gastric protein solubilization kinetics in sunflower meal (SFM) products using porcine digestion simulation model. The SFM samples were derived from diverse processing approaches: 1) dehulled-cold pressed (SFM_CP), 2) dehulled-solvent-extracted (SFM_SE), and 3) application of electrostatic separation technology on SFM_SE to generate high crude protein (CP) version (SFM_SEP). Soybean meal (SBM) was included for reference comparison (Table 1). Considering the complex factors influencing retention time, gastric pH, and pepsin secretion, the study employed multiple sampling times, and pH levels. A total of 500 mg CP equivalent of each sample (in triplicates) was mixed with 25 mL of 0.1 M phosphate buffer (pH 6.0) and 2 mL of pepsin (27 mg/mL). The pH was adjusted to either 1.5, 2.5, 3.5 or 4.5 using 1 M HCl and placed in incubator shaker (200 rpm) at 39°C. Samples were taken at 0, 30, 60, and 90 min, snap-frozen in liquid nitrogen, stored frozen, later thawed at 4°C, centrifuged (15,000 × g for 10 min) and supernatants analyzed for CP. The data were analyzed using Proc GLIMIXX in SAS while Gompertz equation was used to describe the gastric protein solubilization kinetics. The model included the fixed effects of protein source or processing, stomach pH and their interaction on the gastric CP solubility at 90 min and gastric protein solubility kinetics (A-maximum solubilized CP, Wo- initial CP solubility, Ku- solubilization rate, Ti- time to inflection). The analyzed CP SBM, SFM_CP, SFM_SE, and SFM_SEP, were 514.4, 524.4, 393.5, and 484.2 g/kg DM, respectively. Gastric CP solubility increased with lower pH and longer incubation time (P < 0.05), which corresponded well with the optimum pH of pepsin activity around 2. Compared with SFM, SBM had the least (P < 0.05) gastric CP solubility at pH 4.5 and 3.5, and the least predicted maximum gastric CP solubility (A) at pH 4.5, 3.5 and 2.5 (P < 0.05; Table 2). SFM_CP showed the greatest predicted initial gastric CP solubility at 0 h (Wo) and A (P < 0.05). Electrostatic fractionation of SFM_SE (SFM_SEP) enhanced gastric CP solubility at pH 3.5 and 2.5 and reduced the solubility time to inflection point (Ti; P < 0.05). In conclusion, data indicated that cold pressing SFM increased gastric CP solubility relative to solvent extraction. However, electrostatic fractionation of SFM_SE improved protein gastric solubility. While SBM remains a standard, incorporating the studied sunflower meals with their fast CP digestion kinetics in feed formulation could improve protein utilization in young animals with high stomach pH. In vivo studies, particularly on ileal amino acid digestibility, are crucial to validate these findings. Sunflower meal tables_FMN.pdf

Development and characterization of a zeolite based drug delivery system: Application to cannabidiol oral delivery

The growing interest in the therapeutic potential of cannabidiol (CBD) has led to the need for effective and reliable delivery methods that overcome its low oral absorption. Zeolites, a class of porous nanoparticles, offer unique advantages as drug carriers due to their high surface area and adjustable pore size. In this study, a zeolite-based drug delivery system was developed for the encapsulation of CBD. The zeolite particles were characterized using various techniques such as Scanning Electron Microscopy (SEM), N2 adsorption analysis, Solid-state Fourier Transform Infrared (FTIR), Direct Light Scattering (DLS), X-ray diffraction (XRD) and thermogravimetric analysis (TGA) before and after the loading. The drug encapsulation efficiency, and the release profile of CBD from the zeolite matrix were evaluated in addition to in vitro dissolution experiments in the intestinal and gastric simulated fluids. The results showed that the loaded zeolite particles exhibited high encapsulation efficiency of 73.5 %. XRD analysis proved that the USY structure remained intact after loading with CBD. DLS and N2 adsorption analysis indicated that CBD was successfully loaded into the zeolite matrix. When compared to CBD containing particles in a commercialized capsule, the in-vitro dissolution rate of CBD loaded zeolite was significantly higher after 30 min in the simulated stomach (pH 1.8) and the intestinal (pH 6.8) fluids, 67.8 % versus 43.6 % and 62.6 % vs 38.4 % respectively. Our findings open new avenues for the use of zeolites as an efficient drug delivery system for drugs with low bioavailability like CBD.

A microfluidic model for infantile in vitro digestions: Characterization of lactoferrin digestion

We present a miniaturized, flow-through model for infantile in vitro digestions, following up on our previously published in vitro digestive system for adults. Microfluidic ‘chaotic’ mixers were employed as microreactors to help emulate the biochemical processing going on in the infantile stomach and intestine. Simulated digestive fluids were introduced into these micromixers, and the mixtures were incubated for 60 min after both the gastric phase and the intestinal phase. The pH of the infantile stomach was set at 5.3, which is higher than that of adults. This leads to entirely different patterns of digestion for the milk protein, lactoferrin, used in our study as a model compound. It was found that lactoferrin remained undigested as it passed through the gastric phase and reached the intestinal phase intact, unlike in adult digestions. In the intestinal phase, lactoferrin was rapidly digested. Our miniaturized, infantile, in vitro digestive system requires much less labor and chemicals than standard approaches, and shows great potential for future automation.

Assessment of Encapsulated Probiotic Lactococcus lactis A12 Viability Using an In Vitro Digestion Model for Tilapia.

Probiotics face harsh conditions during their transit through the gastrointestinal tract (GIT) of fish because of low-pH environments and intestine fluid. Therefore, the evaluation of probiotic viability under simulated gastrointestinal conditions is an important step to consider for probiotic supplementation in fish feed prior to in vivo trials. Therefore, this study aimed to evaluate the effect of stomach and intestinal simulated conditions on the viability of encapsulated Lactococcus lactis A12 using an in vitro digestion model for tilapia. A Box Behnken design was used to evaluate the potential effect of three factors, namely stomach pH, residence time in the stomach, and enzyme quantity, on the viability of encapsulated Lactococcus lactis A12. As the main results, low pH (4.00), long residence time (4 h), and enzyme quantity (2.68 U of total protease activity) led to lower final cell counts after the phases of the stomach and intestine. Encapsulated probiotic bacteria showed higher viability (p < 0.05) and antibacterial activity (p < 0.05) against the pathogen Streptococcus agalactiae than non-encapsulated bacteria. The results suggest that L. lactis A12 survives in GIT conditions and that the proposed in vitro model could be used to explore the viability of probiotic bacteria intended for fish feed supplementation.

Purified Clinoptilolite-Tuff as an Efficient Sorbent for Food-Derived Peanut Allergens.

The avoidance of allergen intake is crucial for persons affected by peanut allergy; however, the cross-contamination of food is common and leads to unpredictable consequences after the consumption of supposedly "safe" food. The aim of the present study was to eliminate harmful traces of peanut allergens from food using purified clinoptilolite-tuff (PCT)-a specially processed zeolite material. Analyses were performed using a peanut ELISA and a Coomassie blue (Bradford) assay. Mimicking conditions of the human gastrointestinal tract demonstrated a higher efficacy of PCT in the intestine (pH 6.8) than in the stomach (pH 1.5). Adsorption rates were fast (<2 min) and indicated high capacities (23 µg and 40 µg per 1 mg of PCT at pH 1.5 and pH 6.8, respectively). Allergenically relevant peanut protein concentrations were sorbed in artificial fluids (32 µg/mL by 4 mg/mL of PCT at pH 1.5 and 80.8 µg/mL by 0.25 mg/mL of PCT at pH 6.8) when imitating a daily dose of 2 g of PCT in an average stomach volume of 500 mL. Experiments focusing on the bioavailability of peanut protein attached to PCT revealed sustained sorption at pH 1.5 and only minor desorption at pH 6.8. Accompanied by gluten, peanut proteins showed competing binding characteristics with PCT. This study therefore demonstrates the potential of PCT in binding relevant quantities of peanut allergens during the digestion of peanut-contaminated food.

Development of pH-responsive Eudragit S100-functionalized silk fibroin nanoparticles as a prospective drug delivery system.

Silk fibroin nanoparticles (FNP) have been increasingly investigated in biomedical fields due to their biocompatibility and biodegradability properties. To widen the FNP versatility and applications, and to control the drug release from the FNP, this study developed the Eudragit S100-functionalized FNP (ES100-FNP) as a pH-responsive drug delivery system, by two distinct methods of co-condensation and adsorption, employing the zwitterionic furosemide as a model drug. The particles were characterized by sizes and zeta potentials (DLS method), morphology (electron microscopy), drug entrapment efficiency and release profiles (UV-Vis spectroscopy), and chemical structures (FT-IR, XRD, and DSC). The ES100-FNP possessed nano-sizes of ∼200-350 nm, zeta potentials of ∼ -20 mV, silk-II structures, enhanced thermo-stability, non-cytotoxic to the erythrocytes, and drug entrapment efficiencies of 30%-60%, dependent on the formulation processes. Interestingly, the co-condensation method yielded the smooth spherical particles, whereas the adsorption method resulted in durian-shaped ones due to furosemide re-crystallization. The ES100-FNP adsorbed furosemide via physical adsorption, followed Langmuir model and pseudo-second-order kinetics. In the simulated oral condition, the particles could protect the drug in the stomach (pH 1.2), and gradually released the drug in the intestine (pH 6.8). Remarkably, in different pH conditions of 6.8, 9.5, and 12, the ES100-FNP could control the furosemide release rates depending on the formulation methods. The ES100-FNP made by the co-condensation method was mainly controlled by the swelling and corrosion process of ES100, and followed the Korsmeyer-Peppas non-Fickian transport mechanism. Whereas, the ES100-FNP made by the adsorption method showed constant release rates, followed the zero-order kinetics, due to the gradual furosemide dissolution in the media. Conclusively, the ES100-FNP demonstrated high versatility as a pH-responsive drug delivery system for biomedical applications.

PSIII-2 Evaluation of medium-chain fatty acids on just-weaned piglet performance and diarrhea scores: A nursery trial

Abstract Weaning is one of the most stressful events for commercial pigs. The transition from mother’s milk (animal proteins) to a solid diet based on plant proteins, the reduction in lactose intake and the decline in HCl secretion by the digestive system of the piglet result in a sudden and significant increase in stomach pH as well as an increased risk of post-weaning diarrhea. The aim of this trial was to evaluate whether the use of a blend of medium-chain fatty acids (MCFAs) on top-off conventional nursery diets would improve zootechnical performance and intestinal problems in just-weaned piglets. Piglets [n = 624, 21-d of age, 6.5 kg body weight (BW), (♂ Fast Duroc x ♀ Fast 275)] were housed in 26 pens of an experimental nursery. Each pen (24 pigs/pen, with a starting density of 3.0 ft2/pig) was equipped with a height-adjustable water sucker, a water bowl and fitted with a single feeder-bin. Females and males were allocated to each pen, according to 3 BW categories (heavy, medium, and light). During a 46-d period of trial, the piglets (13 replicated pens per treatment) were allotted to a conventional 5 phases feeding program with 2 kg/MT of chlortetracycline (22%) and 400 g/MT of tiamuline (1.78%; CON). These basal diets contained 2,500 ppm Zn in Phases #1, 2, and only 2,000 ppm Zn in phase #3. Phases #1 to 3 were also supplemented with Ca-butyrate (1 kg/MT) and a blend of protected acidifiers (1 kg/MT). The treated group consisted to the basal diet (CON) supplemented with a blend of medium-chain fatty acids (MCFAs) at 1.0 or 0.75 kg/MT for Phases #1, 2,3 and Phases #4, 5, respectively and supplying of a proprietary blend of caprylic, capric, and lauric acids. Daily feed consumption, weekly pig pen BW, dead and removed pigs and daily diarrhea evaluation index were completed. Data are analyzed by an ANOVA model including treatment and pen as fixed and random effects, respectively. Pairwise comparisons were completed with a Chi-square test. The overall results are presented in Table 1. At the end of wk 2 and 3, animals receiving MCFAs had a better average daily gain (ADG; P &amp;lt; 0.05) than CON. Therefore, at wk 2, 3 and 4, MCFAs animals BW were heavier than CON ones (P &amp;lt; 0.05). Average daily feed intake (ADFI) was not significantly different for the overall duration of the trial (P &amp;gt; 0.05). However, at weeks 2 and 3, MCFAs piglets had a greater ADFI than CON ones (P &amp;lt; 0.05). The daily diarrhea index of the MCFAs group was less than CON at wk 3 (P &amp;lt; 0.05). In this trial, the significant improvement of diarrhea index on just-weaned MCFAs treated piglets could explain the significant better growth during the first 3 wk of nursery.

253 The influence of corn-based fiber on digesta short chain fatty acid composition and pH in growing pigs

Abstract Pigs can obtain energy from fibrous feedstuffs through a symbiotic relationship with their gastrointestinal microbiome, which results in the production of metabolites, such as short chain fatty acids (SCFA). An experiment was conducted with the objective of investigating how different insoluble corn-based fiber sources influence changes in SCFA composition along the digestive tract of growing pigs. Two replicates of 28 gilts [n = 56; initial body weight (BW) = 26.7 ± 2.5 kg; PIC800 x Camborough], were randomly assigned to one of 7 semi-synthetic diets. Dietary treatments included a control (CTL) diet with a formulated total dietary fiber (TDF) value of &amp;lt; 1% and 6 diets with a CBF replacing 30% of the corn starch in CTL: dehulled degermed corn (DHDG; TDF = 1.09%), ground corn (COR; TDF = 3.24%), high protein dried distiller’s grains (HP; TDF = 8.79%), dried distiller’s grains (DDGS; TDF = 9.35%), corn gluten meal (CGM; TDF = 9.88%), and corn bran (BRN; TDF = 13.15%). Pigs were individually housed, and limit-fed at 2.4 times maintenance. On d 31, pigs were necropsied, and ileal, cecal, and colonic digesta were collected for immediate SCFA analysis and stomach, jejunal, ileal, and cecal digesta pH was measured. Data were analyzed as a linear mixed model with treatment as a fixed effect, replicate as a random slope or fixed effect, where appropriate, using the mixed procedure of SAS. There were no differences in jejunal nor stomach pH (P ≥ 0.51). Ileal pH was greatest (P = 0.01) in HP, DDGS, and CGM diets. Cecal pH was greatest (P &amp;lt; 0.01) in the BRN diet and lowest in COR and HP. Molar proportions of ileal SCFAs did not differ (P ≥ 0.74) among treatments. In the cecum, molar proportions of butyrate production did not differ (P = 0.74). Cecal acetate proportions were less (P = 0.03) in CTL, COR, and HP compared with all other treatments (51.54, 61.09, 51.92, 52.89, 59.16, 63.87, and 63.32%, for CTL, DHDG, COR, HP, DDGS, CGM, and BRN, respectively). Cecal propionate proportions were greatest (P = 0.01) in BRN and least in DHDG, COR, and CGM (30.85, 27.67, 27.67, 30.91, 30.47, 24.03, and 35.86% for CTL, DHDG, COR, HP, DDGS, CGM, and BRN, respectively). Relative to CTL, isobutyrate proportions in the cecum for COR, HP, and DDGS were reduced by 65%, 52%, and 53%, respectively (P &amp;lt; 0.01). In the colon, there were no differences in molar proportions of acetate, butyrate, nor isobutyrate (P ≥ 0.254). However, HP and CGM had a smaller (P = 0.04) proportion of propionate in the colon and COR and BRN had the greatest proportion of colonic propionate (33.92, 29.68, 38.41, 25.3, 30.00, 26.76, and 37.94% for CTL, DHDG, COR, HP, DDGS, CGM, and BRN, respectively). Collectively, the different fibrous components of CBFs can influence SCFA proportions in the growing pig.

Parthenolide alleviates indomethacin-induced gastric ulcer in rats via antioxidant, anti-inflammatory, and antiapoptotic activities.

Parthenolide (PTL) is a sesquiterpene lactone that occurs naturally. It demonstrates a variety of beneficial effects, such as antioxidant, anti-inflammatory, and antiapoptotic properties. The study investigated the potential protective impact of PTL on indomethacin (INDO) induced stomach ulcers in rats. The rats were classified into 5 distinct categories. Group 1 served as the "control" group. Rats in the second group received a single oral dosage of INDO (50 mg kg-1). Rats inGroups three and four received 20 and 40 mg kg-1 oral PTL 1 h before INDO. Omeprazole (30mgkg-1) was given orally to Group 5 rats 1h before INDO. Pretreatment with PTL increased stomach pH and decreased gastric volume as well as reduced the morphological and histological changes induced by INDO. Analysis of probable pathways showed that pre-treatment with PTL successfully reduced oxidative, inflammatory, and apoptotic consequences caused by INDO. The ingestion of PTL leads to a notable increase in the levels of glutathione reduced (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT). Furthermore, PTL decreased the concentration of malondialdehyde (MDA). In contrast, it was shown that PTL increased both cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2). PTL shows a significant decrease in the expression of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB). PTL therapy resulted in a decrease in Bcl-2-associated X protein (Bax) levels and an increase in B-cell lymphoma 2 (Bcl2) levels. In conclusion, PTL offers gastroprotection by its antioxidant, anti-inflammatory, and anti-apoptotic qualities.

Low fouling and pH-responsive poly(N-vinyl imidazole)/poly(ethylene glycol) methacrylate copolymer gels for colon targeted diclofenac sodium delivery

Protein and cell adhesion onto drug delivery matrices interferes with the predesigned drug delivery profile to the targeted site. Antifouling surfaces are needed to overcome this problem and improve the effectiveness and efficiency of drug delivery systems. Copolymers of N-vinyl imidazole (NVI) with poly(ethylene glycol methacrylate) (PEGMA) were synthesized via free radical polymerization under cryogenic conditions as potential pH-responsive drug delivery systems resistant to protein and cell adhesion. FTIR spectroscopy, elemental analysis, thermal analysis (DSC), mechanical tests, contact angle, surface energy, and SEM analysis provide the physicochemical properties of the samples. Static adsorption/adhesion experiments show that the copolymer cryogels resist BSA adhesion. Furthermore, the copolymer cryogels demonstrate anti-cell adhesion behavior against colon colorectal carcinoma (HCT-116) cells. They are non-cytotoxic toward HDFa fibroblasts. Diclofenac sodium (DS) - loaded copolymer cryogels show pH-dependent sustained drug delivery. The release studies show a limited release in stomach pH (2.0). On the other hand, enhanced release is observed in pH 5.0 and pH 7.4 within 15 h. The quantities of diclofenac sodium released from the copolymer cryogels are sufficient to show anti-inflammatory activity.

Aloe vera gel confers therapeutic effect by reducing pyroptosis in ethanol-induced gastric ulcer rat model: Role of NLRP3/GSDMD signaling pathway

BackgroundGastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore the therapeutic impact of Aloe vera gel on ethanol-provoked GU in rats and to elucidate the underlying mechanisms involved.MethodsAn ethanol-induced GU rat model was constructed using forty male Wistar rats distributed at random into four groups: control, ulcer, pantoprazole, and Aloe vera. Gross evaluation of the stomach, ulcer index (UI), inhibition index, and gastric pH estimation were analyzed. Gastric malondialdehyde (MDA) and reduced glutathione (GSH) were determined using the spectrophotometric method, and serum gastrin level was measured by an enzyme-linked immunosorbent assay. Gastric nucleotide-binding domain, leucine-rich repeat, and pyrin domain PYD containing protein 3 (NLRP3) and gasdermin D (GSDMD) mRNA expression levels were estimated by quantitative real-time PCR. Finally, the histopathological examination of the glandular part of stomach tissue was done.ResultsThe ulcer group revealed a significant increase in MDA, gastrin, NLRP3, and GSDMD and a decrease in gastric pH and GSH compared to the control group. Gross investigations of the ulcer group revealed a hemorrhagic lesion in the stomach and an increase in UI. Also, histopathological results for this group showed severe epithelial loss, haemorrhage, inflammatory cell infiltration, and blood vessel congestion. However, Aloe vera treatment improved the gross, biochemical, molecular, and histopathological alterations induced by ethanol when compared to the ulcer group.ConclusionsAloe vera exerted antiulcer activities through modulation of oxidant/antioxidant status, anti-secretory properties, and mitigation of pyroptosis.

Unravelling pH/pKa influence on pH-responsive drug carriers: Insights from ibuprofen-silica interactions and comparative analysis with carbon nanotubes, sulfasalazine, and alendronate

This study employs density functional theory to explore the interaction between ibuprofen (IBU) and silica, emphasizing the influence of the trimethylsilyl (TMS) functional group for designing pH-responsive drug carriers. The surface (S) and drug (D) molecules' neutral (0) or deprotonated (−1) states were taken into consideration during the investigation. The likelihood of these states was determined based on the pKa values and the desired pH conditions. To calculate the pH-dependent interaction energy (EintpH), four different situations have been identified: S0D0, S0D−1, S−1D0, and S−1D−1.The electrostatic component of interaction energy aligns favorably with its theoretical value in both the Debye-Hückel and Grahame models. The investigation has gathered first-hand experimental data on the drug loading and release of pH-responsive mesoporous silica nanoparticles. Effective drug loading was observed in the acidic environment of the stomach (pH 2–5), followed by a release in the slightly basic to neutral pH of the small intestine (pH 7.4), These findings align with existing literature. The results revealed horizontal drug adherence on silica surfaces, improving binding capabilities. Comparisons were made with combinations involving carboxylated carbon nanotubes and ibuprofen, silica, and sulfasalazine, and silica and alendronate, exploring drug loading/release dynamics associated with positive/negative interaction energies. The investigation, supported by experimental data, contributes valuable insights into pH-responsive mesoporous silica nanoparticles, offering new design possibilities for drug carriers.

Fabrication and physicochemical investigation of pH-responsive alginate/pectin hybrid network hydrogel for improved stability and controlled release of diallyl thiosulfinate

The present investigation explores the formulation and fabrication of alginate-pectin (with varying degree of methoxylation) hybrid network hydrogel beads through ionotropic gelation process as a biocompatible carrier material for encapsulating diallyl thiosulfinate (allicin). The primary aspiration of this research is to overcome allicin's inherent instability which restricts its use in functional food fortification and medicinal products as a bioactive compound with several intriguing health-promoting characteristics. Fabrication of the beads were done through structured parameter optimization. Chemical interaction between allicin and biopolymer matrix was assessed by FTIR-ATR. The ARGE entrapped hydrogel beads had a near spherical shape with sphericity factor ∼1.0 with an average diameter of ∼3.5 mm in the hydrated state (density ∼1.06 g/cm3). The beads showed encapsulation efficiency of ∼70.8 %. The beads efficaciously reduced degradation (<5 %) and stabilized ampule amount of allicin for a prolonged time. Various physicochemical characterizations of the produced beads were done. Further, in vitro release kinetics of allicin from beads were observed in simulated gastrointestinal environment and it showed a sustained release pattern. The release behavior of allicin exhibited a higher release at intestinal pH (∼88 %) than stomach pH (∼35 %). The formulation expressed commendable antimicrobial activity against gram positive and negative bacteria in both solid and liquid media. Moreover, the encapsulation process retained significant antioxidant potential (>60 %). Anti-inflammatory and hemolysis assay expressed admirable biocompatibility. Hence, the results suggest that the fabricated formulation is suitable for being a drug carrier material for allicin while accentuating its aptitude for upholding hemocompatibility, allicin’s concentration, sustained release and bioactivity.

Impact of precursor-derived peracetic acid on post-weaning diarrhea, intestinal microbiota, and predicted microbial functional genes in weaned pigs

Post-weaning diarrhea affects piglets in the nursery phase of production, leading to a substantial impact both at the farm and financial levels. The multifactorial etiology of this disease includes housing conditions, pig genetics, microbial composition, and metagenomic assets. Among the common therapeutic approaches, the widely used zinc oxide underwent a European Union ban in 2022 due to its negative environmental impact and correlation to increased antimicrobial resistance. During this study, we have tested two levels of inclusion of the potential antimicrobial alternative peracetic acid, delivered in water via the hydrolysis of the precursors sodium percarbonate and tetraacetylethylenediamine, in comparison to zinc oxide and an untreated control during a 2-week animal study. We assessed the microbial composition and predicted the metagenome, together with performance and physiological parameters, in order to describe the microbial functional role in etiopathology. Both zinc oxide and peracetic acid resulted in amelioration of the diarrheal status by the end of the trial period, with noticeable zinc oxide effects visible from the first week. This was accompanied by improved performance when compared to the first-week figures and a decreased stomach pH in both peracetic acid levels. A significant reduction in both stomach and caecal Proteobacteria was recorded in the zinc oxide group, and a significant reduction of Campylobacter in the stomach was reported for both zinc oxide and one of the peracetic acid concentrations. Among other functional differences, we found that the predicted ortholog for the zonula occludens toxin, a virulence factor present in pathogens like Escherichia coli and Campylobacter jejuni, was less abundant in the stomach of treated pigs compared to the control group. In water, peracetic acid delivered via precursor hydrolysis has the potential to be a valid intervention, an alternative to antimicrobial, to assist the weaning of piglets. Our findings support the view that post-weaning diarrhea is a complex multifactorial disease with an important metagenomic component characterized by the differential abundance of specific predicted orthologs and microbial genera in the stomach and caecum of pigs.

RSM optimized chitosan based composite hydrogel for sustained drug delivery applications

Hybrid hydrogels with good biocompatibility have practical applications in the field of drug delivery. However, it remains challenging to formulate the hybrid hydrogels for sustained drug release by regulating their pore size and degradation rates. Herein, a hybrid chitosan-alginate hydrogel (superabsorbent) was synthesized using maleic acid as a cross-linker and acrylamide as a grafting agent. The composite hydrogel exhibited a good swelling percentage of 1246% (at pH 10), analysed using response surface methodology (RSM). The hybrid hydrogel system was hemocompatible as well as biocompatible and utilized for drug delivery applications. Pantoprazole sodium was taken as a model drug and it was loaded in the superabsorbent using the swelling diffusion method. The composite hydrogel showed excellent encapsulation efficiency for pantoprazole sodium (99.74%). The intermolecular interactions between hydrogel and drug were examined using different analytical techniques including XRD (X-Ray Diffraction), FTIR (Fourier transform infrared), SEM (Scanning electron microscope), thermal analysis and EDX (Energy dispersive X-ray) mapping. The swelling percentage of the drug loaded hydrogel under simulated gastrointestinal conditions was recorded as 917.80% (at stomach pH 1.2) and 756.95% (at intestinal pH 7.4) where protonation/deprotonation of the drug in the hydrogel matrix played an important role. In vitro drug release from the drug-loaded hydrogel was sustained up to 10 days and correlated with its swelling tendency, displaying higher release profiles at pH 1.2 (99.69%) than at pH 7.4 (72.16%). The pore volume of hydrogel was tuned varying the cross-linker amount during synthesis. BET (Brunauer-Emmett-Teller) results revealed that the pore volume of the hydrogel varied between 0.01775–0.01327 cm3/g for the cross-linker amount between 0.18–0.26 g, respectively. The impact of various factors including amount of cross-linker, pore volume, and drug loading percentage on drug release at pH 1.2 and 7.4 was studied statistically as well as experimentally and these factors significantly controlled the drug release percentage. The drug release from the hydrogel followed the Makoid-Banakar model with Fickian diffusion mechanism. The synthesized composite chitosan-alginate hydrogel could be a promising candidate for its utilization as a sustained drug delivery system.

Chitosan based hybrid superabsorbent for controlled drug delivery application.

In the present study, a hybrid chitosan-alginate superabsorbent is prepared using maleic acid as a cross-linker and acrylamide as a grafting agent using the free radical mechanism. The composite hydrogel shows good swelling capacity along with hemocompatibility and biocompatibility and hence it is utilized as a drug delivery device. The characterization techniques including x-ray diffraction, Fourier transform infrared, x-ray photoelectron spectroscopy, and thermal analysis indicate the successful synthesis of stable hydrogel with rich functionalities. Metformin hydrochloride is used as a model drug which is used to treat diabetes. The drug encapsulation is done using the swelling diffusion method after the synthesis of hydrogel. The release of metformin from the drug-loaded hydrogel at physiological pH highlights the role of non-covalent interactions between the drug and hydrogel. In vitro release studies of Metformin from the drug-loaded hydrogel show higher release profiles at intestinal pH (7.4) compared to stomach pH (1.2). The observed cumulative release is 82.71% at pH 7.4 and 45.67% at pH 1.2 after 10 h. Brunauer-Emmett-Teller analysis reveals the effect of surface area, pore size, and pore volume of hydrogel on the drug release. The drug release from the hybrid chitosan-alginate hydrogel is found to be more sustained in comparison to the pure chitosan hydrogel. For the present drug delivery system, the swelling-controlled release is found to be more dominating than the pH-controlled release. The synthesized hydrogel can be successfully employed as a potential drug delivery system for controlled drug delivery.

Xylooligosaccharide Production From Lignocellulosic Biomass and Their Health Benefits as Prebiotics.

Lignocellulosic biomass (LCB) comprising of wheat bran, coconut husk, rice husk, cereals straw, and other hardwood and softwoods is a good source for the production of xylooligosaccharides (XOS) (prebiotic). XOS produced are nondigestible carbohydrates being stable under stomach pH and digestive enzymes so they can be easily delivered to the intestine in native form, thus stimulating the growth of probiotics. Here we review about the raw material, production, purification, and application of XOS with health benefits. Importance of XOS being valuable food ingredient is increasing as they perform a variety of functions, including reduction in cholesterol levels, gastrointestinal health maintenance, anticancer and antioxidant properties, and modulation of immune system. We also discuss the different characterization methods which are necessary to determine the degree of polymerization (DP) of XOS. Low DP (xylobiose and xylotriose) is usually preferred for the application of XOS in various sectors. This review emphasizes the growing significance of XOS as a prebiotic, serving as nourishment for probiotics.

In vivo Assessment of Diltiazem HCl Immobilized Co-polymeric pH Sensitive Microgels

Novel stimuli responsive coplymeric (2-ethyl hexyl acrylate -co- itaconic acid diltiazem HCl loaded microgels were fabricated and characterized successfully to reduce the degradation of drugs in acidic pH of stomach resulting in reduced bioavailability to minimize dosing frequency and enhance patient compliance. To evaluate the clinical significance, in-vivo studies of recently prepared novel pH sensitive copolymeric microgels are performed and different pharmacokinetic parameters as maximum plasma concentration (Cmax), time to reach the maximum plasma concentration (Tmax), area under the plasma concentration-time curve (AUC 0-?), half-life (t 1/2?) and elimination rate constant (K21) are analyzed. The mean plasma concentration of sustained release DLZ loaded microgels showed higher Tmax for prepared microgels (4.0758±0.22 hrs) than standard drug solution. The half-life t1/2? of test microgels is relatively higher (5.68±5.86 hrs) whereas the Cmax is measured to be 41.06±2.02ng/ml for microgels with AUC0-? calculated as 460.35±39.99 ng.hr/ml. Elimination rate constant K21 for DLZ microgels is 0.18 ± 0.07 hrs-1 for which showed the absorption phase is extended and drug is present for a prolong period of time in the body. This study proved that novel prepared pH sensitive copolymeric p(EHA-co-IA) microgels released model drug in sustained release manner in pH sensitive medium.