Functional and Genomic Insights into Clostridium butyricum MCC0233: Probiotic Features and Safety Assessment.

The precursors of Mg-Al hydrotalcite (Mg/Al-LDHs-NO3) were prepared by low saturation coprecipitation method (constant pH method). In addition, alsine-intercalated magnesium-aluminum hydrotalcite (LDHs-Ala) was synthesized by low saturation coprecipitation (constant pH) and nucleation/crystallization isolation methods when the pH value was higher than the isoelectric point of alanine. The release properties of alanine intercalated hydrotalc in simulated gastric fluid (hydrochloric acid solution with pH=1.5) and intestinal fluid (phosphate solution with pH=7.4) were measured by spectrophotometer in vitro. The results showed that LDHs-Ala had good slow-release properties in simulated intestinal fluid and gastric fluid in vitro. Then sodium alginate was used to coated alanine intercalated hydrotalc for slow release in simulated intestinal fluid and simulated gastric fluid. It can be concluded that the coated intercalated hydrotalc has a low slow release rate in gastric fluid, but has a good slow release performance in simulated intestinal fluid. It can be concluded that the coated intercalated hydrotalc is expected to be a intestinal targeted release agent, which can be applied in biomedicine.

Mesoporous tablet-shaped potato starch aerogels for loading and release of the poorly water-soluble drug celecoxib

Biodegradable hydrophilic gelatin microspheres containing the anticancer drug methotrexate (MTX) of different mean particle sizes (1-5, 5-10, and 15-20 microns) were prepared by polymer dispersion technique and crosslinked with glutaraldehyde. The microspheres were uniform, smooth, solid and in the form of free-flowing powder. About 80 per cent of MTX was incorporated in gelatin microspheres of different sizes. The in vitro release of MTX was investigated in two different media, namely simulated gastric and intestinal fluids. The release profiles indicated that gelatin microspheres released MTX in a zero-order fashion for 4-6 days in simulated gastric fluid and for 5-8 days in simulated intestinal fluid. The rate of release of MTX decreased with increase in the particle size of the microspheres. MTX release was faster in gastric fluid when compared to intestinal fluid.

Nanoparticles have the potential to increase bioavailability of nutraceutical compounds such as (-)-epigallocatechin gallate (EGCG). Ovalbumin was conjugated with dextran using the Maillard reaction. The resultant ovalbumin-dextran (O-D) conjugates were self-assembled with EGCG to form EGCG O-D conjugate nanoparticles at pH 5.2 after heating at 80 °C for 60 min. Ovalbumin in EGCG O-D conjugate nanoparticles was further cross-linked by glutaraldehyde for 24 h at room temperature. EGCG O-D conjugate nanoparticles and cross-linked EGCG O-D conjugate nanoparticles in aqueous suspension had particle sizes of 285 and 339 nm, respectively, and showed a spherical morphology. The loading efficiencies of EGCG in these two nanoparticles were 23.4 and 30.0%, whereas the loading capacities were 19.6 and 20.9%, respectively. These nanoparticles showed positive zeta-potentials in a pH range from 2.5 to 4.0 but had negative charges at pH ≥5.0. EGCG O-D conjugate nanoparticles maintained a particle size of 183-349 nm in simulated gastric fluid (SGF) and 188-291 nm in simulated intestinal fluid (SIF) at 37 °C for 2 h, whereas cross-linked nanoparticles had particle sizes of 294-527 nm in SGF and 206-300 nm in SIF. Limited release of EGCG was observed in both nanoparticle systems in simulated gastric and intestinal fluids without and with digestive enzymes. EGCG O-D conjugate nanoparticles significantly enhanced the apparent permeability coefficient (Papp) of EGCG on Caco-2 monolayers compared with EGCG solution, suggesting that these nanoparticles may improve the absorption of EGCG.

The qualitative and quantitative evaluation of eleven brands of piroxicam capsules marketed in Nigeria is presented. The disintegration time, dissolution rate and absolute drug content were determined in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF) without enzymes. Weight uniformity test was also performed according to official methods. Data obtained from the dissolution profiles in both media (SIF and SGF) were mathematically treated according to the model proposed by Khan (with slight modification) and the resulting predicted availability equivalent (PAE) was used to quantitatively assess/ predict bioavailability of piroxicam from the various brands. Our results indicate variable PAE with pH. In SGF, four out of the eleven (11) brands could be adjudged to be bioequivalent with the innovator drug, Feldene (Neimeth, Nigeria); In SIF, only three out of the eleven (11) were equivalent with the innovator drug. All the capsules (except one brand) generally disintegrated within 15 min. in both SIF and SGF. The weights were also very uniform with insignificant variations. However, the variation in absolute drug contents were generally wide, with all the capsules having drug contents that are above the label claim Key Words: Piroxicam, Qualitative, Quantitative Evaluation Bio-Research Vol.1(2) 2003: 101-110

Deoxynivalenol (DON) occurs in many commonly used cereal grains. Pigs feed with DON concentrations as low as 0.6–2.0 mg/kg can result in reduced feed intake and growth rate, damage to intestinal epithelial cells, and increase susceptibility to enteric pathogens. Sodium metabisulfite (SMBS) can efficiently detoxify DON by converting it 8-DONS or 10-DONS in vitro. However, if SMBS is added directly to the feed, SMBS rapidly degrades under acidic aqueous conditions (e.g. pig stomach) and little SMBS is delivered to the intestinal absorption site where it can effectively detoxify DON. Thus, the objective of this study was to encapsulate SMBS into Eudragit L100-55 nanofibrous mats to deliver intact SMBS to the small intestine and evaluate the efficacy of DON detoxification in the simulated intestine fluid (SIF) using an in vitro intestinal epithelial cell (IPEC-J2) model. Nanofibrous mats were produced by coaxial electrospinning, with peak loading capacity and loading efficiency of SMBS reaching 32.00% and 80.01%. DON-induced cytotoxicity was not observed during in vitro analysis consisting of incubation of DON in the presence of SMBS-containing nanofibers (0.5% w/w) in simulated gastric fluid (SGF) for 2 h followed by incubation in a mixture of SGF and SIF (1:1) for 20 min. Meanwhile, compared to the DON treatment, incubation of DON in the presence of SMBS-containing nanofiber (0.5% w/w) in SGF for 2 h and SIF for 20 min decreased the gene expression of inflammatory cytokines in the IPEC-J2 cells and maintained the cell integrity. To conclude, SMBS released from Eudragit L100-55 nanofibrous mats in the SIF effectively decreased the adverse effects induced by DON in the IPEC-J2 cells. Nanofibrous mats can release a large amount of SMBS in a short time in SIF to achieve the effect of detoxifying DON.

This study aimed at evaluating some quality control parameters to compare the quality, safety, and efficacy of nine br ands of ofloxacin tablets available in the Nigerian market. The physicochemical parameters and assay of the nine brands of ofloxacin tablets were assessed through the evaluation of uniformity of tablet weight, friability, hardness, disintegration, and assay of active ingredients according to established methods. The dissolution rate and disintegration time were determined in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) without enzymes. The concepts of dissolution efficiency (DE) and predicted availability equivalence (PAE) were used to estimate the likely in vivo bioavailability. All brands complied with the official specification for uniformity of weight, friability, and disintegration. The disintegration test revealed that the drugs had higher disintegration times in SGF (7.0 ± 0.95) relative to those in SIF (5.0 ± 2.55). The dissolution profiles in SGF showed that only one sample attained 70% dissolution in less than 45 min and the other 5 samples in 1 h, while in SIF, four samples attained 70% dissolution in 45 min and all samples in 1 h. The UV spectrophotometric assay of ofloxacin tablets revealed that three samples contained over 95% (w/w) of labeled chemical content. The PAE in SGF indicated over 90% release from five samples, while it revealed over 70% release in SIF from three samples out of the aforementioned. Only four of the brands considered in this study demonstrated comparable quality standards. The method is simple and rugged for both routine analysis and evaluation of the dissolution pattern of ofloxacin tablets as in vitro tests for batch-to-batch quality control assessment.

The fruit and hulls of the water caltrop (Trapa taiwanensis Nakai) are used as hepatoprotective herbal tea ingredients in Taiwan. The stability of hydrolysable tannins in herbal drinks has rarely been reported. In the present study, two hydrolysable tannins, tellimagrandin II (TGII) and 1,2,3,4,6-pentagalloylglucopyranose (PGG), were isolated from water caltrop hulls. The stability of the two compounds was evaluated by treatment with various pH buffer solutions, simulated gastric fluid and intestinal fluid, different temperatures, and photo-irradiation at 352 nm in different solvents. Results showed that TGII and PGG were more stable in a pH 2.0 buffer solution (with 91.88% remaining) and in a water solution with 352 nm irradiation (with 95% remaining). TGII and PGG were more stable in methanol or ethanol solutions (with >93.69% remaining) than in an aqueous solution (with <43.52% remaining) at 100 °C. In simulated gastric fluid, more than 96% of the hydrolysable tannins remained after incubation at 37 °C for 4 h. However, these hydrolysable tannins were unstable in simulated intestinal fluid, as after incubation at 37 °C for 9 h, the content of TGII had decreased to 31.40% and of PGG to 12.46%. The synthetic antioxidants, butyl hydroxy anisole (BHA), di-butyl hydroxy toluene (BHT), and propyl gallate, did not exhibit photoprotective effects on these hydrolysable tannins. However, catechin, a natural antioxidant, displayed a weak photoprotective effect. Ascorbic acid had a short-term thermal-protective effect but not a long-term protective effect. The different stability properties of hydrolysable tannins in solutions can be used in the development of related herbal teas in the future.

Lunasin and BBI (Bowman Birk protease inhibitor) are bioactive soy peptides that have been shown to be effective suppressors of carcinogenesis in in vitro and in vivo model systems. Since they are subject to digestion in the gastrointestinal tract, we investigated here the stabilities of lunasin and BBI to digestion in vitro by simulated intestinal fluid (SIF) and simulated gastric fluid (SGF). Samples containing lunasin and BBI of varying purities were subjected to in vitro digestion by SIF and SGF at different times and analyzed by Western blot. While the pure BBI reaction is stable after SIF and SGF digestions, the purified lunasin from soybean and synthetic lunasin are easily digested after 2 min in both in vitro digestions. In contrast, lunasin from soy protein containing BBI is comparatively stable after SIF and SGF digestions. Both lunasin and BBI are able to internalize into the cell and localize in the nucleus even after digestion, suggesting that some of the peptides are intact and bioactive. These data suggest that BBI plays a role in protecting lunasin from digestion when soy protein is consumed orally. The role of other soy protease inhibitors such as Kunitz Trypsin Inhibitor (KTI) cannot be excluded from these experiments.

Degradation of poly( d,l-lactic acid) nanoparticles coated with albumin in model digestive fluids (USP XXII)

Clostridioides difficile is the leading cause of nosocomial infections and a worldwide urgent public health threat. Without doubt, there is an urgent need for new effective anticlostridial agents due to the increasing incidence and severity of C. difficile infection (CDI). The aim of the present study is to investigate the in vivo efficacy of auranofin (rheumatoid arthritis FDA-approved drug) in a CDI mouse model and establish an adequate dosage for treatment. The effects of increased C. difficile inoculum, and pre-exposure to simulated gastric intestinal fluid (SGF) and simulated intestinal fluid (SIF), on the antibacterial activity of auranofin were investigated. Auranofin’s in vitro antibacterial activity was stable in the presence of high bacterial inoculum size compared to vancomycin and fidaxomicin. Moreover, it maintained its anti-C. difficile activity after being exposed to SGF and SIF. Upon testing in a CDI mouse model, auranofin at low clinically achievable doses (0.125 mg/kg and 0.25 mg/kg) significantly protected mice against CDI with 100% and 80% survival, respectively. Most importantly, auranofin (0.125 mg/kg and 0.25 mg/kg) significantly prevented CDI recurrence when compared with vancomycin. Collectively, these results indicate that auranofin could potentially provide an effective, safe and quick supplement to the current approaches for treating CDI.

Oral delivery of insulin from alginate/chitosan crosslinked by glutaraldehyde

Development of enteric-coated, biphasic chitosan/HPMC microcapsules for colon-targeted delivery of anticancer drug-loaded nanoparticles

Protection of Bifidobacterium lactis and Lactobacillus acidophilus by microencapsulation using spray-chilling

In present research work, we report the synthesis, in vitro hydrolysis study and pharmacological evaluation of new mutual prodrugs of mefenamic acid (MA) and 1,2 dihydro-1,5-dimethyl-4-(1-methylethyl)-2-phenylpyrazol-3-one with the aim of improving the therapeutic potency and retard the adverse effects of gastrointestinal origin. The structure of the synthesized mutual ester prodrugs (MP1 and MP2) were confirmed by IR, 1H NMR, 13C NMR, mass spectroscopy and their formation was confirmed by TLC. The purity of the synthesized compounds was established by elemental analysis. The title compounds were tested for analgesic activity by acetic acid-induced writhing method; anti-inflammatory activity was tested by carrageenan-induced rat paw edema method and ulcerogenicity. The study of the analgesic activity revealed that both prodrugs (MP1 and MP2) have shown significant reduction (81.67, 63.90 %) in writhing response produced by acetic acid as compared to parent drug MA (61.10 %). Both mutual prodrugs showed better maximum anti-inflammatory effects (71.43, 85.71 %) and for longer time as compared to parent drug MA (53.14 %). The synthesized prodrugs were also found to be very less irritating to gastric mucosal membrane than parent drugs. The kinetics of ester hydrolysis was studied in simulated gastric fluid (SGF) at pH 1.2 and simulated intestinal fluid (SIF) at pH 7.4. The release of free MA from prodrugs showed negligible hydrolysis in SGF as compared to SIF. This indicated that prodrugs were sufficiently stable at pH 1.2 and do not break in the stomach, but release MA in SIF.