Artificial Intestinal Fluid Research Articles

Development of microcrystalline cellulose based hydrogels for the in vitro delivery of Cephalexin

Three hydrogels namely, microcrystalline cellulose (MCC), microcrystalline cellulose-carboxymethyl cellulose (MCC-CMC) and microcrystalline cellulose-xylan (MCC-xylan) are synthesized using ethylene glycol diglycidyl ether as crosslinker. For the chemical characterization, FT-IR spectroscopy is adopted, whereas gel fraction and swelling ratio are used for the physical characterization of the hydrogels. Coarse morphology of hydrogels is further visualized by microscopic observation. The rheological characterization proves that MCC-CMC gel withstands higher strain to resist permanent deformation than the other two gels. The hydrogels are used for the loading and in vitro release of Cephalexin. The in vitro delivery is carried out in various simulated body fluids such as phosphate buffer saline (PBS), artificial intestinal fluid (AIF) and artificial gastric fluid (AGF). MCC-CMC is observed to deliver Cephalexin individually 15% in AGF, 86% in AIF, 98% in PBS and 98% in consecutive buffers (AGF followed by AIF and PBS).

PH-responsive hydrogels based on the self-assembly of short polypeptides for controlled release of peptide and protein drugs

In this study, a pH-responsive hydrogel consisting of a 4-arm poly(ethylene glycol)-block-poly(L-glutamic acid) (4a-PEG-PLG) copolymer was developed and used for the controlled release of peptide and protein drugs. It was found that the mechanical properties and degradation processes of the hydrogels could be tuned by changing the polymer concentrations. In vitro drug release results revealed that the release of insulin (or BSA) from hydrogel was highly dependent on the pH, i.e., less than 20% of insulin (or BSA) was released in the artificial gastric fluid (AGF) at 72 h, while close to 100% of insulin (or BSA) was released in the artificial intestinal fluid (AIF). It was because that the deprotonation of carboxyl groups in PLG block caused the disassembly, and even disintegration of the hydrogel in AGF, thereby resulting in accelerated drug release. Circular dichroism spectra showed that the bioactivities of insulin and BSA released from hydrogels were obviously unchanged compared to those of native insulin and BSA, respectively. Mouse fibroblast L929 cells were cultured on the surface of hydrogels and the viabilities of cultured cells were above 90% after incubation for 24 h, indicating that the hydrogels had good cytocompatibilities. Moreover, in vivo degradation evaluation disclosed that the formed hydrogels will completely degrade after 8 days, and the H&E staining study demonstrated the excellent biocompatibility of the as-prepared hydrogels. Therefore, the biocompatible and biodegradable 4a-PEG-PLG hydrogel may serve as a promising platform for pH-responsive drug delivery.

Chitosan-modified lipid nanodrug delivery system for the targeted and responsive treatment of ulcerative colitis

Targeted and sensitive drug release at the colitis site is critical for the effective therapy of ulcerative colitis and reduction of side effects from the drug. Herein, we used 3,3′-dithiodipropionic acid (DTPA) to covalently link quercetin (Qu) and glyceryl caprylate-caprate (Gcc) via ester bonds to prepare Qu-SS-Gcc lipid nanoparticles (Qu-SS-Gcc LNPs). Dexamethasone (Dex) was used as a model drug, and chitosan (CSO) was modified on the surface of Qu-SS-Gcc LNPs to obtain CSO-modified Dex-loaded Qu-SS-Gcc LNPs (CSO/Dex/LNPs). The encapsulation efficiency and drug loading of CSO/Dex/LNPs were 93.1 % and 8.1 %, respectively. The in vitro release results showed that CSO/Dex/LNPs had esterase-responsive characteristics and could release the drug rapidly in esterase-containing artificial intestinal fluid. A human colorectal adenocarcinoma cell (Caco-2) monolayer was used as the intestinal cell barrier model. Transmembrane resistance measurements and permeation experiments showed that CSO/Dex/LNPs had a protective effect on the lipopolysaccharide (LPS)-stimulated Caco-2 cell monolayer and increased the expression of E-cadherin in LPS-stimulated Caco-2 cells. Moreover, CSO/Dex/LNPs could significantly reduce the expression of the inflammatory factors TNF-α, IL-6 and NO in LPS-stimulated RAW 264.7 cells. The ulcerative colitis mouse model was constructed by using C57BL/6 mice. The in vivo distribution results showed that CSO/Dex/LNPs had colon-targeting effects and strong retention ability in the colons of mice with colitis. The results also showed that CSO/Dex/LNPs had better anti-inflammatory effects than free Dex, which could reduce colonic atrophy, reduce histomorphological changes and increase the expression of E-cadherin in the colon. Furthermore, the expression levels of TNF-α, IL-6 and NO in the CSO/Dex/LNP-treated group were 37.4 %, 35.5 % and 33.2 % of those in mice with colitis, respectively.

Effects of oligosaccharides on the growth and stress tolerance of Lactobacillus plantarum ZLP001 in vitro, and the potential synbiotic effects of L. plantarum ZLP001 and fructo-oligosaccharide in post-weaning piglets1.

In this study, we evaluated the effects of seven oligosaccharides on the growth rate and stress tolerance of Lactobacillus plantarum ZLP001 in vitro, and the potential synbiotic effects of the most effective oligosaccharide [fructo-oligosaccharide (FOS)] and L. plantarum ZLP001 on the growth performance, apparent nutrient digestibility, fecal microbiota, and serum immune index in weaning piglets. Most oligosaccharides were utilized as carbohydrate sources by L. plantarum ZLP001, but we observed obvious differences in the bacterial growth depending on oligosaccharide type and concentration. Oligosaccharides and glucose significantly alleviated the decrease in L. plantarum ZLP001 viability in artificial gastric fluid, whereas none of the sugars affected viability in artificial intestinal fluid. FOS and galacto-oligosaccharide significantly improved the viability of L. plantarum ZLP001 under heat stress (65 °C for 15 and 30 min). FOS and soybean oligosaccharide significantly increased the viability of L. plantarum ZLP001 in response to cold stress (4 °C for 30 and 60 days). On the basis of the findings of in vitro experiments, we selected FOS for in vivo studies. Eighty-four weaned piglets were randomly assigned to one of the following groups: control (basal diet, no additives), freeze-dried L. plantarum ZLP001 (4.2 × 109 CFU/g, 2 g/kg diet), FOS (5 g/kg diet), and combination (0.2% L. plantarum ZLP001 + 0.5% FOS). Body weight and feed consumption were recorded for determinations of the average daily gain (ADG), average daily feed intake (ADFI), and feed-to-gain ratio (F/G). On day 28, fresh fecal samples were collected to evaluate the apparent digestibility of nutrients and microbiota, and serum samples were collected to determine the immune status. L. plantarum ZLP001 plus FOS significantly increased ADG and decreased the F/G ratio compared with the no-additive control. The combination treatment also increased the apparent nutrient digestibility of dry matter and crude protein. Compared with the control and single supplementation, the combination treatment had a significant regulatory effect on the intestinal microbiota, as evidenced by increases in Lactobacillus spp. and a decrease in Enterobacteriaceae. In addition, the combination treatment increased the concentrations of serum IFN-γ and immunoglobulin G. In conclusion, FOS can be utilized well by L. plantarum ZLP001 and can be combined with it as a potential synbiotic that shows synergistic effects in weaning piglets.

Carboxymethyl Cellulose-Xylan Hydrogel: Synthesis, Characterization, and in Vitro Release of Vitamin B12.

The current work reports the synthesis of carboxymethyl cellulose (CMC) and xylan-based homopolymerized as well as copolymerized hydrogels using an ethylene glycol diglycidyl ether cross-linker in alkaline medium. The hydrogels are physically characterized by the swelling ratio and gel fraction. The morphological observation of hydrogels reveals the porous structure for the copolymerized gels. The rheological behavior of the gels elaborates that the copolymerized CMC–xylan gel synthesized in a 1:1 molar ratio has superior strain-bearing ability and possesses the shortest gelation temperature and time. Vitamin B12 here is used as the model vitamin to be loaded in the hydrogels and subsequent studies involving the in vitro release in artificial gastric fluid (AGF, pH = 1.2), artificial intestinal fluid (AIF, pH = 6.8), and phosphate-buffered saline (PBS, pH = 7.4). The synthesized gels show a cumulative release of 19–28% in AGF, 80–88% in AIF, and 93–98% in PBS, independently. Further, the highest cumulative release of 93–99% is recorded for all gels when in vitro release is performed in successive buffers, that is, first in AGF, followed by AIF and PBS.

Development of a gelatin‐g‐poly(acrylic acid‐co‐acrylamide)–montmorillonite superabsorbent hydrogels forin vitrocontrolled release of vitamin B12

ABSTRACTGelatin (Ge)‐g‐poly(acrylic acid‐co‐acrylamide) and montmorillonite (MMT)‐clay‐based nanocomposite hydrogels were fabricated to study the controlled release of vitamin B12. Polymeric hydrogels were characterized with Fourier transform infrared (FTIR) spectroscopy, X‐ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). FTIR spectroscopy confirmed the grafting of partially neutralized acrylic acid on a Ge backbone. The incorporation of MMT fillers inside the nanocomposite hydrogels and their increased crystallinity were established by XRD analysis. The rough surface morphologies of the composite hydrogels shown by SEM resulted from the assimilation of MMT inside the same. TEM confirmed the formation of nanosized composites. The average length and width of the MMT platelets were found to be 184.37 and 20.48 nm, respectively. The maximum swelling of the hydrogel was 375 g/g, and the results were established with Design‐Expert software. The biodegradability of the nanocomposite increased in comparison to that of the copolymer hydrogel. Biocompatibility and cytotoxicity studies were also performed. During different time intervals, the controlled release of vitamin B12in artificial gastric fluid (AGF) and artificial intestinal fluid (AIF) was evaluated with a UV–visible spectrophotometer; this resulted in different controlled release curves. The release in AGF was 42%, and in AIF, the cumulative release was 80% over 6 h. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2019,136, 47596.

New glucose oxidase-immobilized stimuli-responsive dextran nanoparticles for insulin delivery

Designing strategies for the use of biopolymer-based nanoparticles as drug delivery carriers is a considerable challenge in pharmaceutical science. Present study reports synthesis of a novel glucose responsive and in-vitro pH triggered insulin delivery system comprised of glucose oxidase immobilized on acryloyl crosslinked dextran dialdehyde (ACDD) nanoparticles. Scanning electron microscopy, transmission electron microscopy and particle size analysis data revealed that these carriers possess nanosize which is an important parameter for drug delivery applications. In-vitro insulin release studies were performed under artificial gastric fluid (AGF, pH 1.2) and artificial intestinal fluid conditions (AIF, pH 7.4) at physiological temperature (37 °C). Insulin release profile showed controlled release of about 70% under AIF conditions for 24 h. Insulin release mechanism studied using different kinetic models revealed that Korsmeyer-Peppas model appropriately explained the mechanism as ʻnon-Fickian’ diffusion release of insulin. These glucose responsive stimuli sensitive nanocarriers exhibited controlled release of about 90% under AIF conditions in the presence of glucose. These findings revealed that these nanoparticles are promising and reliable delivery systems to overcome problems related with subcutaneous insulin therapy.

Effects of tannins in Galla Chinensis on pharmacokinetics of rifampicin in vivo and in vitro

This study was aimed to explore the effects of tannins in Galla Chinensis on rifampicin in vivo. In the experiment in vitro, UV spectrophotometry and high performance liquid chromatography (HPLC) were used to investigate the solubility of rifampin in pH 1.3, 6.8, artificial gastric juice environment and artificial intestinal fluid environment as well as the effects of tannins on solubility of rifampin in the above conditions. In the experiment in vivo, the process of rifampicin was studied after intragastric administration of rifampicin and rifampicin+ tannins in Galla Chinensis, and then the pharmacokinetic parameters were calculated. The results showed that rifampicin was constantly precipitated in the artificial gastric juice environment over time, and nearly 85% of the rifampicin was precipitated after 6 hours; it showed a good solubility in the artificial intestinal juice environment. After adding the said tannins, the concentration of rifampicin was decreased significantly in both environments, and the concentration of rifampicin in artificial intestinal juice remained relatively stable, while that in artificial gastric juice remained the original downward trend. The pharmacokinetic parameters displayed that as compared with rifampicin alone, AUC0-t and Cmax were decreased significantly, MRT0-t slowed down significantly, Tmax doubled to 7.0 h and the bioavailability was only 31.65% in rifampicin + tannins in Galla Chinensis group. The experiment indicated rifampicin had a poor solubility in acidic environment and the decrease of bioavailability of rifampicin when in combination with tannin was mainly due to the reduction of rifampicin solubility in intestinal tract by complexation of rifampicin with tannin, thus affecting its absorption in intestinal tract. Therefore, rifampicin and the Chinese herbal medicines or Chinese patent medicines rich in tannin should not be taken simultaneously.

In vitro assessment of pyrethroid bioaccessibility via particle ingestion

Due to their intensive use in agricultural and residential pest control, human exposure to residues of multiple pyrethroids frequently occurs. Pyrethroids have exceptionally high affinity for solid particles, highlighting the need to understand human exposure through oral ingestion of contaminated soil or dust particles. In this study, we used artificial gastrointestinal fluids to measure the desorption or bioaccessibility of eight current-use pyrethroids in soil and dust samples. Tenax was further included as a sink in parallel treatments to simulate the effect of removal due to transfer of pyrethroids to lipid membranes. The use of 0.4 g of Tenax in 20 mL digestive fluids resulted in rapid and efficient trapping of pyrethroids, and further, greatly increased bioaccessibility. In the artificial digestive fluids without Tenax, 6.0–48.0% of pyrethroids were desorbed over 21 h, and the fractions increased by 1.6–4.1 folds to 21.5–79.3% with the Tenax sink. Therefore, 6.0–79.3% of soil or dust-borne pyrethroids may be considered bioavailable upon ingestion. While protein and sucrose increased the estimated bioaccessibility, co-presence of lipid (vegetable oil) decreased the bioaccessibility of pyrethroids, likely due to competitive phase partition. Pyrethroids were also found to be unstable in the artificial intestinal fluid containing pancreatin, further decreasing the potential bioaccessibility of pyrethroids on soil or dust particles. The limited bioaccessibility should be considered to refine the prediction of human exposure and risk through oral ingestion of pyrethroid residues.

Enzyme-Resistant Dextrin from Chinese Yam Starch for Potential Application in Beverage Industry: Preparation, Physicochemical Properties and In Vitro Digestion

Preparation conditions, physicochemical properties and in vitro digestibility of enzyme-resistant dextrin from Chinese yam starches, which are native, easily accessible and cheap raw materials in China, were investigated in the current study. The results showed that the enzyme-resistant fraction content in enzyme-resistant dextrin increased and the whiteness of the enzyme-resistant dextrin decreased with the increasing concentrations of hydrochloric and citric acids and the rising heating temperatures, and the prolonged heating times. Considering the manufacturing cost and the beneficial usage, the enzyme-resistant dextrin produced by heating of Chinese yam starch in the presence of hydrochloric (0.11% dsb) and citric (0.2% dsb) acids at 150°C for 60min was selected. Enzyme-resistant dextrin had a low molecular weight of about 6800 Da and rich “non-digestible” α-1,2 glycosidic bond and was well-soluble in water, stable at pH 3.0–7.0 or after heating at 85°C for 0.5 h showed, high thermal stability and high resistant to the artificial gastric juice and small intestinal fluids. These characteristics make the selected enzyme-resistant dextrin suitable for use in the soft drink industry as the soluble dietary fibres and prebiotics in the beverages. This would provide an excellent opportunity to reduce the caloric value of the beverages and exert a beneficial effect on the intestinal microflora of people consuming beverages enriched with enzyme-resistant dextrins.

Co-existing colloidal phases in artificial intestinal fluids assessed by AF4/MALLS and DLS: A systematic study into cholate & (lyso-) phospholipid blends, incorporating celecoxib as a model drug

Colloidal phases (self-assemblies) in aqueous dispersions of selected binary bile salt/phospholipid blends were studied utilizing the combined analytical approach of asymmetrical flow field-flow fractionation (AF4) and multi-angle laser light scattering (MALLS) in order to resolve the co-existence of different colloidal assemblies. The binary blends were prepared by freeze-drying from tert-butanol/water co-solvent solutions. The blends contained one of two bile salts (sodium taurocholate (TC) or sodium glycodeoxycholate (GDX)) and a mono- or di-acyl phospholipid (lyso-phosphatidylcholine (L-PC) and phosphatidylcholine (PC), respectively). Bile salt and phospholipid (PL) concentrations and their respective ratios were varied systematically within the physiological range found in human intestinal fluids. Furthermore, the BCS class II drug Celecoxib was incorporated in selected blends to assess its potential impact on colloidal phases. To further investigate the smallest self-assemblies observed in AF4/MALLS analysis, dispersions of TC and GDX, respectively, were prepared and analyzed by dynamic light scattering (DLS).AF4/MALLS analysis revealed that binary bile-salt/phospholipid blends form three distinct particle fractions, when the concentration of bile-salt was sufficiently high (≥3.5 mM). Those fractions were assumed to be very small pure bile-salt dimeric/oligomeric self-assemblies (Ø ≈ 2–3 nm), mid-sized mixed micelles (Ø ≈ 10–50 nm) and large liposomes/aggregates (Ø ≈ 150–280 nm). If present, Celecoxib was found solubilized within the structures, but at the lowest TC concentration triggered the formation of an additional (vesicular) phase.

Synthesis of carboxymethyl cellulose-g-poly(acrylic acid)/LDH hydrogel for in vitro controlled release of vitamin B 12

Abstract pH-sensitive nanocomposite hydrogels were synthesized from carboxymethyl cellulose-g-poly(acrylic acid) and LDH (Layered Double Hydroxide). Polymeric hydrogels were characterized using FTIR, XRD, SEM, EDX, TEM, DLS, TGA and DSC. The grafting of partially neutralized acrylic acid (AAc) on carboxymethyl cellulose (CMC) backbone was confirmed by FTIR. XRD has confirmed the presence of LDH fillers inside the nanocomposite hydrogels. Scanning Electron Microscopy (SEM) showed rough surface morphology resulting from incorporation of LDH in the composite hydrogels. Transmission Electron microscopy (TEM) and Dynamic Light Scattering (DLS) confirmed the formation of the nanosized composite. Thermal property of the hydrogels was improved with the incorporation of LDH. Higher swelling was observed in basic pH medium. Controlled release of vitamin B12 in artificial gastric fluid (AGF) and in artificial intestinal fluid (AIF) was evaluated during different time periods using an UV–visible spectrophotometer. In vitro release profile of the drugs in various pH conditions, resulted in different controlled release curves.

高效液相色谱法研究二氢齐墩果酸在人工胃液和肠液中的稳定性

高效液相色谱法研究二氢齐墩果酸在人工胃液和肠液中的稳定性

Effect of Cys, GSH, and pH on Mercury Release from Tibetan Medicine Zuotai, β-HgS, and α-HgS in Artificial Gastrointestinal Juices.

Zuotai, also named as "gTso thal", a known Tibetan medicinal mixture containing insoluble cubic crystal mercuric sulfide (β-HgS), has been used to treat diseases with long history. The mercury release ratio from Zuotai in gastrointestinal environment is one determinant factor for its bioavailability and biological effect. However, the information is still scarce now. Therefore, the study was designed to investigate the effect of sulfhydryl biomolecules [L-cysteine (Cys) and glutathione (GSH)] and pH on mercury dissociation from Zuotai, β-HgS, and hexagonalcrystalmercuric sulfide(α-HgS) in artificial gastrointestinal juices or pure water with a 1:100 solid-liquid ratio. And, the digestion and peristalsis of gastrointestinal tract were simulated in vitro. The results showed the following trend for the mercury release ratio of Zuotai, artificial gastric juice>artificial intestinal juice>pure water, whereas the trend for β-HgS and α-HgS was as follows, artificial intestinal fluid>artificial gastric fluid>pure water. The mercury release ratios of Zuotai, β-HgS, and α-HgS significantly increased in artificial intestinal juice containing L-Cys or GSH compared to those without sulfhydryl biomolecules in the juice. However, in contrast to the results observed for β-HgS and α-HgS, the mercury release ratio of Zuotai was reduced remarkably in pure water and artificial gastric juice with Cys or GSH. And, we found that strong acidic or strong alkaline environments promoted the dissociation of mercury from Zuotai, β-HgS, and α-HgS. Taken together, current findings may contribute to other studies regarding clinical safety and bioavailability of the traditional drug Zuotai containing β-HgS.

Investigation on stability and degradation kinetics of febrifugine

To investigate the stability and degradation kinetics of febrifugine. The results showed that within 24 hours, febrifugine content was decreased by only 1% in mobile phase solvent, but its content was decreased to be 90% of the initial content in the water, methanol, 50% methanol and 10% acetonitrile solution. When the pH value of the solution was between 3 and 7, the retention rate of febrifugine in 24 hours was over 98%, but its content was decreased by about 12% in alkaline solution (pH 9.0). The higher the temperature, the worse the stability of febrifugine. At 40-80 ℃, the content of febrifugine was decreased to be 60% of its initial content in 10 hours, but the content was decreased by only 5% in 10 h at 20 ℃.However, no matter 40 ℃or 60 ℃, febrifugine was mainly transformed into isofebrifugine, and the total content of febrifugine and isofebrifugine was equal to their initial total content in 10 hours, while incase of 80 ℃, the total content was decreased to be 83.33% in 10 h, which suggested that the structure of febrifugine was absolutely changed, not just isomerized to be isofebrigugine at high temperature. Light had a significant impact on the stability of febrifugine. Under bright light, the content of febrifugine was reduced by about 23% in 108 h, but it only decreased by about 10% in the natural light or darkness. In artificial gastric fluid (pH 1.4) and artificial intestinal fluid (pH 6.8), the content of febrifugine was decreased by less than 5% in 10 h. After storage at high temperature(60 ℃), high humidity [(75±1)%] and strong light (3 000 lx) conditions for 10 d, the content of solid febrifugine was decreased by 0.27%, 7.6% and 5.39%, respectively. The degradation of febrifugine basically complied with the first-order reaction kinetic process in the following conditions: in water, methanol, 50%methanol and 10% acetonitrile solvents, alkaline solution (pH>7), different light intensity and different temperatures (20,40 ℃). Therefore, no matter the isolation and purification of febrifugine or the production of the related preparations, it should be done fast in the acidic solution, low temperature and dark conditions, while the febrifugine solid should be kept in dry and dark conditions.

Synthesis of pH-responsive N-acetyl-cysteine modified starch derivatives for oral delivery

In this study, a novel type of pH-responsive polymer PyHES-NAC (2-hydroxy-3-(2-propynyloxy) propyl hydroxyethyl starch (PyHES)) – (N-acetyl-cysteine (NAC)) was synthesized. First, PyHES was prepared via hydrophobic modification of hydroxyl groups in hydroxyethyl starch (HES) with propynylglycidyl ether (PGE), and then pH-responsive carboxylic acid group was connected to propynyl group via thiol-yne click reaction with NAC. Aqueous PyHES-NAC solutions exhibited a good transference between hydrophobic (or self-assembly) and hydrophilic static along with the change of pH value and protective properties of drugs under acidic conditions. 10.0% DOX was released under artificial gastric fluid after 2 h, whereas an immediate release (above 80%) was observed under artificial intestinal fluid. Drug loading capacity of PyHES-NAC was increased by the increase of degree of substitution (DS) of hydrophobic propynyl groups in PyHES, and 41 wt% DOX Loading capacity was the highest value in our study area.

Optimization of Aqueous Extraction and Biological Activity of Harpagophytum procumbens Root on Ex Vivo Rat Colon Inflammatory Model.

Harpagophytum procumbens has a long story of use for the treatment of inflammatory diseases. Considering both the antiinflammatory effects of H. procumbens in multiple tissues and the stability of harpagoside in artificial intestinal fluid, the aim of the present study was to explore the possible protective role of a microwave-assisted aqueous Harpagophytum extract (1-1000μg/mL) on mouse myoblast C2C12 and human colorectal adenocarcinoma HCT116 cell lines, and isolated rat colon specimens challenged with lipopolysaccharide (LPS), a validated ex vivo model of acute ulcerative colitis. In this context, we evaluated the effects on C2C12 and HCT116 viability, and on LPS-induced production of serotonin (5-HT), tumor necrosis factor (TNF)-α, prostaglandin (PG)E2 and 8-iso-prostaglandin (8-iso-PG)F2α . Harpagophytum extract was well tolerated by C2C12 cells, while reduced HCT116 colon cancer cell viability. On the other hand, Harpagophytum extract reduced H2 O2 -induced (1mM) reactive oxygen species (ROS) production, in both cell lines, and inhibited LPS-induced colon production of PGE2 , 8-iso-PGF2α , 5-HT and TNFα. Concluding, we demonstrated the efficacy of a microwave-assisted Harpagophytum aqueous extract in modulating the inflammatory, oxidative stress and immune response in an experimental model of inflammatory bowel diseases (IBD), thus suggesting a rational use of Harpagophytum in the management and prevention of ulcerative colitis in humans. Copyright © 2017 John Wiley & Sons, Ltd.

Physicochemical properties and stability of the emulsion prepared with various emulsifiers for enteral nutrition preparations

ABSTRACTThe mean diameter of emulsion droplets prepared using three different emulsifiers (egg yolk lecithin alone, egg yolk lysolecithin alone, and a mixture of egg yolk lecithin and lysolecithin) was investigated. Considering the nasal administration of enteral nutrients or that through gastric/jejunal fistulae, the stability of each emulsion with artificial gastric fluid (pH 1.2) or intestinal fluid (pH 6.8) was investigated. When adding artificial intestinal fluid, all emulsions prepared with various emulsifiers (egg yolk lecithin, egg yolk lysolecithin, soybean lecithin, soybean lysolecithin, DK ester® F-140, and Sunsoft® A-141E) were stable. On the other hand, when adding artificial gastric fluid, emulsions prepared with egg yolk lysolecithin or Sunsoft® A-141E were stable, but there was a reduction in the stability of emulsions prepared with the other emulsifiers, with an increase in the particle size. Based on these results, we prepared an emulsion using a natural component-derived emulsifier for enteral nutrients, egg yolk lysolecithin, and clarified the pH change-related stability of the emulsion.

Facile preparation of pH-responsive polyurethane nanocarrier for oral delivery

This study reports a novel one pot synthesis of pH-responsive nanocarrier for oral delivery of hydrophobic drug under gastrointestinal tract. Triblock copolymer MPEG-HTPB-MPEG was synthesized coupling of MPEG and HTPB using hexamethylene diisocyanate(HDI) and pH-responsive carboxylic acid group was attached to polybuthadiene backbone by thiol-ene click reaction in a facile and convenient procedure. The MPEG-HTPB (g-COOH)-MPEG block copolymers were self-organized into micelle assemblies in the water. The size and shape of the micelle assemblies were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The nanocarriers have high drug loading ability for poorly water-soluble drug. The pH-responsive profile was demonstrated by pH-dependent swelling and in vitro drug release. <10.0% IBU was released under artificial gastric fluid after 2h, whereas an immediate release was observed under artificial intestinal fluid. The XTT assay indicated that the micelle obtained from PEG-HTPB (g-COOH)-PEG triblock copolymer are safe in a wide range of concentrations. The results show that pH-responsive PEG-HTPB (g-COOH)-PEG triblock copolymers are promising nanocarriers for the oral administration of hydrophobic drugs.

Inhibition of cholesterol transport in an intestine cell model by pine-derived phytosterols

We have quantified the inhibition of intestinal cholesterol transport by pine-derived phytosterols using an HT29-MTX intestine cell model that forms a mucus layer similar to that in the intestine. An artificial intestinal fluid consisting of digested fat, bile salt, cholesterol, and phytosterols was formulated in order to mimic the conditions in the intestine. The apparent permeability coefficient (Papp) of the positive control, i.e., 0.1mM of cholesterol solubilized in the artificial intestine fluid, was found to be 0.33 (±0.17)×10−6cm/s. When 0.1mM β-sitosterol was solubilized alongside, Papp was effectively zero, corresponding to a total inhibition of cholesterol transport. A similar strong inhibition was found when commercial pine-derived phytosterols, PinVita™ FSP DuPont, were co-solubilized with cholesterol in the dietary model micelles, leading to Papp=0.06 (±0.06)×10−6cm/s, i.e., 5.5 times lower than the cholesterol positive control. Additionally, the effect of potential oral administration formulations generated by the pine-derived phytosterols was also characterized. The formulations were produced as a liquid formulation of the cholesterol-containing artificial intestine fluid. Six liquid formulations were tested of which four displayed a Papp in the range of 0–0.09×10−6cm/s. The remaining two formulations did not show any inhibition effect on cholesterol transport and even enhanced cholesterol transport. It was furthermore observed that the phytosterols were found in the collected intestine cells but not transported to the basolateral region in the intestinal cell model system.