Artificial Intestinal Juice Research Articles

Resveratrol nanodispersion with high stability and dissolution rate

Resveratrol is a highly polyphenolic substance which possesses extensive physiological activities. However, its application is limited by light instability and poor aqueous solubility. In this paper, resveratrol nanodispersion with high light stability and water dissolution rate was prepared by a combination of antisolvent precipitation in the presence of nontoxic polymer and spray-drying. The active ingredients of the unprocessed raw resveratrol decreased 80 wt% when exposed to sun light directly, while that of the resveratrol nanodispersion only reduced 14 wt% at the same condition. The resveratrol nanodispersion dissolved completely in less than 45 min, while raw resveratrol didn't dissolve completely after 120 min. Meanwhile, resveratrol nanodispersion exhibited better antioxidant activity compared to that of raw resveratrol when added in artificial intestinal juice. This study is helpful to promote the application of resveratrol and provides a routine for enhancing stability and water solubility of photosensitive lipophilic materials.

Preparation of the Intestinal-Lysis and Multi-Probiotics Microcapsule

The intestinal-lysis and multi-probiotics microcapsule of L.lactis, L.plantarum and B.bifidum was produced with gelatin and chitosan as wall material by emulsified condensation method. The effects of temperature and the artificial simulation gastric and intestinal juices on the activity of probiotics were investigated. The experimental results show that the storage time of the bacteria was prolonged and the survival rates of the bacteria in the stomach and the intestine were increased by the formation of microcapsule to embed the bacteria, which can play a target action and reduce the production cost.

Study on stability of major pharmaceutical ingredients of Vladimiriae Radix before and after being roasted in artificial gastric juice, artificial intestinal juice and isolated rat gastric, intestinal or colonic incubation juice

To study the stability of costunolide (COS) and dehydrocostus lactone (DEH) of Vladimiriae Radix before and after being roasted in artificial gastric juice, artificial intestinal juice and isolated rat gastric, intestinal or colonic incubation juice. The HPLC method was used for the determination of the mass concentration of COS and DEH Vladimiriae Radix before and after being roasted artificial gastric juice, artificial intestinal juice and isolated rat gastric, intestinal or colonic incubation juice. The samples were incubated with isolated rat stomach, small intestine; colon was used to study physical adsorption, absorption or degradation parameters. COS of Vladimiriae Radix before or after being roasted was unstable in artificial gastric juice, with the average degradation constants as 0.758 0 and 0.531 1. Having been roasted, it showed an increasing stability with a significant difference (P < 0.01). Both of COS and DEH of Vladimiriae Radix before or after being roasted showed high adsorption, uptake or degradation (2 h), and it had significant difference between different parts. COS was unstable in artificial gastric juice (unprocessed Vladimiriae Radix has a higher degradation rate). Isolated rat stomach, small intestine, colon can adsorb, take, degrade COS and DEH of Vladimiriae Radix before or after roasting process obviously and differently. It provides basis for studies on the absorption mechanisms of effective ingredients of Vladimiriae Radix before and after being roasted.

Release characteristics of doxycycline chitosan nanoparticles freeze-dried powderin vitroandin vivo

This paper is to study the release characteristics of doxycycline (DC) raw material drug and doxycycline chitosan nanoparticles (DC-CS-NPs) freeze-dried powder in vitro and in vivo by ultraviolet spectrophotometry and ultra performance liquid chromatography, respectively. Results showed that the release behaviors of DC raw material drug were simulated the most in the zero order dynamic equation in artificial gastric juice, artificial intestinal juice and pH 7.4 buffer phosphate. The release of DC raw material drug was fast which could completely dissolve in one hour; The DC-CS-NPs freeze-dried powder had a significant slow-release characteristic. The release behaviors were simulated the most in the biexponential equation. The drug released fast in the early stage while it released slowly later. The order of release speed of DC-CS-NPs freeze-dried powder from fast to slow was pH 2.0 artificial gastric juice, pH 3.0 artificial gastric juice, pH 4.0 artificial gastric juice, artificial intestinal juice and pH 7.4 buffer phosphate. When DC raw material drug became DC-CS-NPs freeze-dried powder, after a single oral administration at a dose of 20 mg/kg at (25±1) ℃, the double-peak phenomenon of plasma in channel catfish was turned into single-peak, and the pharmacokinetic parameters of DC-CS-NPs freeze-dried powder were changed. Compared to DC raw material drug, the peak concentration (Cmax) decreased. The peak time (Tmax) and terminal elimination half-life (T1/2β) prolonged. The area under concentration-time curve (AUC) was larger. The DC-CS-NPs freeze-dried powder will become an ideal DC new formulation.

In vitro release and in vitro&amp;ndash;in vivo correlation for silybin meglumine incorporated into hollow-type mesoporous silica nanoparticles

BackgroundThe purpose of this study was to develop a sustained drug-release model for water-soluble drugs using silica nanoparticles.MethodsHollow-type mesoporous silica nanoparticles (HMSNs) were prepared using Na2CO3 solution as the dissolution medium for the first time. The water-soluble compound, silybin meglumine, was used as the model drug. The Wagner–Nelson method was used to calculate the in vivo absorption fraction.ResultsThe results of transmission electron microscopy and nitrogen adsorption revealed that the empty HMSNs had uniformly distributed particles of size 50–100 nm, a spherical appearance, a large specific surface area (385.89 ± 1.12 m2/g), and ultralow mean pore size (2.74 nm). The highly porous structure allowed a large drug-loading rate (58.91% ± 0.39%). In 0.08 M Na2CO3 solution, silybin meglumine-loaded HMSNs could achieve highly efficacious and long-term sustained release for 72 hours in vitro. The results of in vitro–in vivo correlation revealed that HMSNs in 0.08 M Na2CO3 solution had a correlation coefficient R2 value of 0.9931, while those of artificial gastric juice and artificial intestinal juice were only 0.9287 and 0.7689, respectively.ConclusionThe findings of in vitro–in vivo correlation indicate that HMSNs together with Na2CO3 solution could achieve an excellent linear relationship between in vitro dissolution and in vivo absorption for 72 hours, leading to a promising model for sustained release of water-soluble drugs.

Fabrication of magnetic drug-loaded polymeric composite nanofibres and their drug release characteristics

Magnetic polymer nanofibres intended for drug delivery have been designed and fabricated by electrospinning. Magnetite (Fe3O4) nanoparticles were successfully incorporated into electrospun nanofibre composites of two cellulose derivatives, dehydroxypropyl methyl cellulose phthalate (HPMCP) and cellulose acetate (CA), while indomethacin (IDN) and aspirin have been used as model drugs. The morphology of the neat and magnetic drug-loaded electrospun fibres and the release characteristics of the drugs in artificial intestinal juice were investigated. It was found that both types of electrospun composite nanofibres containing magnetite nanoparticles showed superparamagnetism at room temperature, and their saturation magnetisation and morphology depend on the Fe3O4 nanoparticle content. Furthermore, the presence of the magnetite nanoparticles did not affect the drug release profiles of the nanofibrous devices. The feasibility of controlled drug release to a target area of treatment under the guidance of an external magnetic field has also been demonstrated, showing the viability of the concept of magnetic drug-loaded polymeric composite nanofibres for magneto-chemotherapy.

PLGA Nanoparticles Improve the Oral Bioavailability of Curcumin in Rats: Characterizations and Mechanisms

The overall goal of this paper was to develop poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) of curcumin (CUR), named CUR-PLGA-NPs, and to study the effect and mechanisms enhancing the oral bioavailability of CUR. CUR-PLGA-NPs were prepared according to a solid-in-oil-in-water (s/o/w) solvent evaporation method and exhibited a smooth and spherical shape with diameters of about 200 nm. Characterization of CUR-PLGA-NPs showed CUR was successfully encapsulated on the PLGA polymer. The entrapment efficiency and loading rate of CUR were 91.96 and 5.75%, respectively. CUR-PLGA-NPs showed about 640-fold in water solubility relative to that of n-CUR. A sustained CUR release to a total of approximately 77% was discovered from CUR-PLGA-NPs in artificial intestinal juice, but only about 48% in artificial gastric juice. After oral administration of CUR-PLGA-NPs, the relative bioavailability was 5.6-fold and had a longer half-life compared with that of native curcumin. The results showed that the effect in improving oral bioavailability of CUR may be associated with improved water solubility, higher release rate in the intestinal juice, enhanced absorption by improved permeability, inhibition of P-glycoprotein (P-gp)-mediated efflux, and increased residence time in the intestinal cavity. Thus, encapsulating hydrophobic drugs on PLGA polymer is a promising method for sustained and controlled drug delivery with improved bioavailability of Biopharmaceutics Classification System (BCS) class IV, such as CUR.

β-galactosidase Determination by an Electrochemical Biosensor Mediated with Ferrocene

Abstract: In this paper, a new viewpoint on the activity determination of β-galactosidase is reported. Glucose oxidase was directly immobilized on a glassy carbon electrode and mediated by ferrocene. The biosensor's performance was based on mediated electron transfer by ferrocene, which reduced via glucose oxidase reaction. In this reaction, substrate of glucose oxidase, glucose was provided by the activity of β-galactosidase in the sample. The parameters of the fabrication process for the electrode were optimized. Experimental conditions influencing the biosensor performance, such as pH, ferrocene and lactose concentrations, and temperature, were investigated and assessed. Finally, the biosensor was successfully applied to determination of β-galactosidase activity of artificial intestinal juice.

Protective effect of whey cheese matrix on probiotic strains exposed to simulated gastrointestinal conditions

A probiotic whey cheese added with Lactobacillus casei LAFTI®L26, Lactobacillus acidophilus LAFTI®L10 or Bifidobacterium animalis Bo was subject in vitro to sequential conditions that parallel the four major steps of digestion: mouth (artificial saliva), oesophagus–stomach (artificial gastric juice), duodenum (artificial intestinal juice) and ileum; its manufacture followed the traditional cheesemaking protocol of Portuguese Requeijão. MRS broth was inoculated in parallel as reference medium, to ascertain the protective effect of the whey cheese matrix itself upon those strains in every digestion step. Mouth conditions had an almost negligible effect upon all three strains, whereas oesophagus–stomach, duodenum and ileum conditions decreased the viable numbers of L. casei and L. acidophilus; in both systems, B. animalis suffered only slight decreases in viable numbers; and L. casei and L. acidophilus behaved likewise in MRS exposed to duodenum and ileum conditions. Whey cheese matrices thus appeared to protect the aforementioned three strains during transit throughout the simulated gastrointestinal system, so they are promising carriers of those probiotic bacteria.

Influence of the coating formulation on enzymatic digestibility and drug release from 5-aminosalicylic acid pellets coated with mixtures of high-amylose starch and Surelease® intended for colon-specific drug delivery

Background: Colon-specific delivery of drugs can be achieved with dosage forms coated with biopolymers that are metabolized selectively by the colonic microflora and yet resistant to enzymatic digestion in the small intestine. Aim: The aim of this study was to study the influence of formulation factors on the performance of mixed films from high-amylose starches and Surelease®, applied using a spray-coating process, as potential colon-specific delivery devices. Methods: 5-Aminosalicylic acid-loaded pellets were prepared by an extrusion-spheronization process and film coated with mixtures of the starches and Surelease®. Optimization of the coating formulation, that is, starch-to-Surelease® ratio, film-coating thickness, and type of starch, was undertaken first in enzyme-free media resembling the conditions in the stomach and small intestine. The effect of curing of the film coating on the drug release profile upon storage was also evaluated. Optimized coating formulations were further assessed for enzymatic digestibility using artificial gastric and intestinal juices containing commercially available pepsin and pancreatin or α-amylase from hog pancreas, respectively. Finally, drug release was assessed in fluid-simulating conditions in the colon (SCF) containing Bacillus licheniformis α-amylase. Results: Film coatings comprising high-amylose starches and Surelease® in a ratio of 1:2 (w/w) and film thickness of approximately 45 μm were able to withstand the chemical and enzymatic environment of the upper gastrointestinal tract, in particular, resisted degradation by the pancreatic α-amylases. Stability of the coatings during storage was achieved with additional curing. In SCF, these coatings were susceptible to enzymatic degradation. Conclusions: This study showed that high amylose starch-mixed films can be successfully used as colon-specific delivery devices. The preparation of the coating dispersions described is simple and rapid, without the need to extract the amylose component of starch.

Enhanced gastrointestinal absorption of N3-O-toluyl-fluorouracil by cationic solid lipid nanoparticles

This study was aimed to prepare N3-O-toluyl-fluorouracil (TFu) loaded cationic solid lipid nanoparticles (TFu-SLNs) and evaluate the potential of a novel lipid-based drug delivery system to enhance the oral absorption of TFu. TFu-SLNs were prepared by the film dispersion-ultrasonication method, using hexadecyltrimethylammonium bromide as cationic tenside. The formulation and manufacture parameters were optimized concerning the drug encapsulation efficiency and the particle size. The in vitro release characteristics, in vivo pharmacokinetic properties and bioavailability, and in situ intestinal absorption features were investigated. The morphology of TFu-SLNs was approximately spherical and the mean particle size was 178.8 ± 9.99 nm; the zeta potential was +19.54 ± 0.32 mV. The mean entrapment efficiency and drug loading were 71.03 ± 1.19% and 3.57 ± 0.08%, respectively. The release behaviors of TFu from TFu-SLNs in PBS were fitted to the bioexponential model, while in artificial gastric juice, artificial intestinal juice and artificial gastric juice (2 h) followed by artificial intestinal juice (2–48 h) were fitted to the Weibull equation. The results of the pharmacokinetic studies in mice showed that the bioavailability of TFu-SLNs was significantly increased compared with that of the TFu suspensions after oral administration. The absorption of TFu-SLNs in intestine of rat was fitted to first-order kinetics with passive diffusion mechanism and the main segments of TFu-SLNs absorbed in intestine were duodenum and jejunum for the bioadhesion mediated by electrostatic interaction between the positively charged colloidal particles and the negatively charged mucosal surface. These results indicated that cationic SLNs would offer a promising delivery system for the facilitation of the bioavailability of poorly oral absorption drugs by enhancing the bioadhesion between the absorption mucosal surface and the drug carriers.

Controlled release of alpha-lipoic acid through incorporation into natural polysaccharide-based gel beads

Abstract Alpha-lipoic acid (ALA) is an essential cofactor for mitochondrial multi-enzyme complexes related to energy production. However, it is unstable under light and heat and its biological half-life ( t 1/2 ) is short. In this study, ALA was incorporated into alginic acid (Alg) gel beads to achieve stabilisation and sustained release. The cationic polymer chitosan (CS) was also added to the Alg gel beads to better control ALA release. In artificial gastric juice (pH 1.2), ALA release from the Alg gel beads was controlled through simple diffusion from the gel matrix. However, in artificial intestinal juice (pH 6.8), the Alg gel beads were immediately disintegrated. On the other hand, Alg gel beads with CS were not disintegrated in artificial intestinal juice (pH 6.8), and achieved pH-independent sustained release of ALA through an electrostatic interaction between the carboxyl groups of Alg and the amino groups of CS. ALA contained within the Alg gel beads was protected from light (UV) and heat (65 °C) compared with ALA alone. Addition of CS to the Alg gel beads further increased the stability of ALA. Thus, stabilisation and controlled release of ALA was achieved through incorporation of ALA in Alg gel beads containing CS.

Synthesis of dehydroabietic acid-modified chitosan and its drug release behavior

A new type of chitosan derivative, dehydroabietic acid-modified chitosan (DAMC), was synthesized by the acylation reaction of chitosan with dehydroabietic acid chloride (DHAC) under microwave irradiation. The resulting product (DAMC) was characterized by FT-IR, UV, 1H NMR, X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and elemental analysis. The degree of substitution (DS) of DAMC was 16.5%. And chitosan and DAMC were used as carriers of fenoprofen calcium (FC), and their controlled release behavior in artificial intestinal juice was studied. The results showed that the controlled release of FC from the carrier of DAMC is better than that from original chitosan.

β-Galactosidase monitoring by a biosensor based on Clark electrode: Its optimization, characterization and application

β-Galactosidase is an hydrolase enzyme that catalyzes the hydrolysis of β-galactosides into monosaccharides. Substrates of different β-galactosidases include ganglioside GM1, lactosylceramides, lactose, and various glycoproteins. A novel aspect of the activity determination of β-galactosidase was presented. A glucose oxidase biosensor based on Clark electrode was utilized in order to monitor β-galactosidase. Immobilization of glucose oxidase was made by gelatin and glutaraldehyde as cross-linker. Several parameters such as glucose oxidase activity, gelatin amount, and glutaraldehyde percentage for cross-linking were optimized. The most important parameter, lactose concentration in working buffer was studied in detail. Optimum temperature, thermal stability, optimum pH, buffer system and its concentration effect on the biosensor system, repeatability, reproducibility, and storage and operational stabilities of the biosensor were identified. A linear detection range for β-galactosidase was observed between 9.4 × 10 −5 and 3.2 × 10 −2 U/ml. Finally, β-galactosidase activity in artificial intestinal juice was investigated by the biosensor and the results obtained were compared with a reference spectrophotometric method.

Preparation and characterization of the graft copolymer of chitosan with poly[rosin-(2-acryloyloxy)ethyl ester

Graft copolymerization of rosin-(2-acryloyloxy)ethyl ester (RAEE) onto chitosan (Cts) was carried out under microwave irradiation using potassium persulfate as an initiator. The structures, morphology, and thermal properties of the Cts graft copolymer (Cts-g-PRAEE) were characterized by means of FT-IR, XRD, SEM, and TG. Also, Cts and Cts-g-PRAEE copolymer were used as carriers of fenoprofen calcium (FC), and their controlled release behavior in artificial intestinal juice were studied. The results show that the rate of release of fenoprofen calcium from the carrier of Cts-g-PRAEE copolymer becomes very slower than that of Cts in artificial intestinal juice.

Electrospun hydroxypropyl methyl cellulose phthalate (HPMCP)/erythromycin fibers for targeted release in intestine

AbstractUltrafine fiber mats of hydroxypropyl methyl cellulose phthalate (HPMCP) were successfully electrospun and explored as drug delivery vehicles using erythromycin as a model drug. The morphology of the electrospun fiber and the drug release process in the artificial gastric juice and in the artificial intestinal juice were investigated. With the same drug‐to‐matrix ratio (HPMCP/erythromycin = 9/1), all the fibers were electrospun into a tape‐like or ribbon shape and the average fiber diameter (AFD) was increased with the HPMCP concentration. Because of the pH‐sensitive property of HPMCP, erythromycin was released from the erythromycin‐containing electrospun HPMCP fiber mats by a slowly diffusion process in the artificial gastric juice, while it was released in nearly first‐order kinetics in the artificial intestinal juice because of the first‐order kinetics dissolution of the HPMCP fibers in the artificial intestinal juice. And the rate of erythromycin released in the artificial intestinal juice was about more than 2.5 times faster than that in the artificial gastric juice. The diameter of the fibers plays an important role on the rate and the total amount of the drug released both in stomach and in intestine, the rate and the total amount of the drug released decreasing with increasing AFD. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007

Effect of microencapsulation on viability and other characteristics in Lactobacillus acidophilus ATCC 43121

Lactobacillus acidophilus ATCC 43121 were microencapsulated with sodium alginate by dropping method. The effects of microencapsulation on the changes in survival rate of the L. acidophilus ATCC 43121 during exposure to artificial gastrointestinal and on the change in heat susceptibility of L. acidophilus ATCC 43121 during the heat treatment were studied. In addition, cholesterol assimilation and intestinal adhesion of non-encapsulated and encapsulated L. acidophilus ATCC 43121 were also investigated to explore the effect of microencapsulation on health beneficial effect of lactic acid bacteria. Non-encapsulated cells were completely destroyed when exposed to artificial gastric juice (AGJ) of pH 1.2 and 1.5, while the treatment declined the viable count of encapsulated samples only by 3 log. Encapsulated cells exhibited a significantly higher resistance to artificial intestinal juice (AIJ) and heat treatment than non-encapsulated samples. The assimilative reductions of cholesterol by non-encapsulated and encapsulated L. acidophilus ATCC 43121 were 35.98% and 32.84%, respectively. However, encapsulation did not significantly ( P>0.05) affect the adherence of L. acidophilus ATCC 43121 onto the human intestinal epithelial cell lines HT-29. The microencapsulation effectively protected the microorganisms from heat and acid treatment in delivering the viable cells to intestine without any significant adverse effect on their functionalities.

Uptake of Polycyclic Aromatic Hydrocarbons by Insoluble Dietary Fiber

The sorption isotherms of polycyclic aromatic hydrocarbons (PAHs) by insoluble dietary fiber (IDF) were measured in artificial gastric juice (AGJ) and artificial intestinal juice (AIJ) at 37◦C and then the sorption behavior of IDF was examined. Benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, and benzo[a]pyrene were used. It was suggested that the uptake of PAHs by carboxymethyle cellulose (CMC), agar, and IDF from powdered young barley leaves (YBL) involved not single sorption behavior, but complex sorption behavior. YBL had an extraordinarily high sorption capacity (60.7–147.3 nmol/g in AGJ and 76.7–162.7 nmol/g in AIJ), as compared with CMC (1.5–3.6 nmol/g in AGJ and 1.1–2.7 nmol/g in AIJ) and agar (0.1–0.4 nmol/g in AGJ and 0.3–0.7 nmol/g in AIJ) at a residual concentration of 5.0 nM. The sorption of PAHs in AGJ and the desorption of PAHs from IDF in both AGJ and AIJ indicate that the sorbed PAH molecules are held firmly by IDF while it passes through the digestive tract in vivo. From the results on sorption capacity and the removability of PAHs from IDF, YBL would be expected to be more useful than CMC and agar.

Low-cost in vitro Screening Method for Digestibility of Pet Chews

Four pet chew treats from four different manufacturers were tested for digestibility using in vitro tests in artificial gastric (stomach) and intestinal juices. In vitro tests were selected to determine the digestibility of dog chews for humane reasons and were conducted under conditions that were designed to simulate the digestive system of dogs. The purpose of the tests was to rapidly and inexpensively determines the rate of degradation of a dog chew in the canine digestive tract to assess product safety for dogs. Dog chew pet treats that are swallowed whole, or in part, should degrade rapidly in the canine digestive system to prevent potentially dangerous blockage. Tests were conducted on one cm and one-half cm cubes of dog chew products. Results of the tests clearly indicated that one product outperformed all others in short-term (under 4 hrs) digestive tests. The Bone-A-Mint Wheat Free formula degraded more rapidly than all other products in tests simulating canine gastric and intestinal juices. Tests conducted in this study will form the basis of an in vitro procedure that can be used as an industry standard to asses the safety of pet chew treats.

Protective Effect of Microencapsulation Consisting of Multiple Emulsification and Heat Gelation Processes on Immunoglobulin in Yolk

: Two different emulsification methods involving multiple emulsification and heat gelation were used for preparation of whey protein-based microcapsules containing immunoglobulin in yolk (IgY). The residual activity of IgY during the emulsion preparation and the effects of microencapsulation on IgY stability under harsh conditions were investigated. The residual activity of IgY in an emulsion prepared with a membrane emulsifier was higher than for an emulsion using a homogenizer. Microencapsulated IgY showed remarkable stability against both pepsin and acid. Both microencapsulated IgY and nonencapsulated IgY were relatively stable in bile and artificial intestinal juice. Microencapsulated IgY retained 74% of initial activity during heat treatment. There were no significant differences in the residual activities of microencapsulated IgY under storage temperatures of 4, 25, and 37°C.