A Pharmacokinetic Study of Mix-160 by LC-MS/MS: Oral Bioavailability of a Dosage Form of Citroflavonoids Mixture.

This study was performed to evaluate and compare the pharmacokinetic parameters between two dosage formulations of hesperidin and naringenin: mixture and tablet. Our objective was to determine that the flavonoid tablet does not significantly modify the pharmacokinetic parameters compared with the mixture. For this study, we administered 161 mg/kg of either mixture (Mix-160) or tablet composed of hesperidin and by intragastric administration. Blood microsamples were collected from tail vein up to 24 h. Serum flavonoid extraction was performed by solid phase extraction and analyzed by LC-MS/MS of triple quadrupole (QqQ). Serum concentration vs. time plot showed that data fitted for a first-order model. The pharmacokinetic parameters were calculated by a noncompartmental model. The results showed that the absorption constant is higher than the elimination constant. The first concentration was found at five minutes, and minimal concentration at 24 h after administration, suggesting a enterohepatic recirculation phenomena and regulation of liver cytochromes' activity. We did not find meaningful differences between the pharmacokinetic parameters of both samples. We concluded that tablet form did not interfere with the bioavailability of hesperidin and naringenin, and it could be a suitable candidate for developing a drug product.

Effect of the rigid segment content on the properties of segmented polyurethanes conjugated with atorvastatin as chain extender.

Segmented polyurethanes were prepared with polycaprolactone diol as soft segment and various amounts of 4,4´-Methylenebis(cyclohexyl isocyanate) and atorvastatin, a statin used for lowering cholesterol, in order to obtain SPU with different content of rigid segments. Polyurethanes with 35% or 50% of rigid segment content were physicochemically characterized and their biocompatibility assessed with L929 fibroblasts. High concentrations of atorvastatin were incorporated by increasing the content of rigid segments as shown by FTIR, Raman, NMR, XPS and EDX. Thermal and mechanical characterization showed that polyurethanes containing atorvastatin and 35% of rigid segments were low modulus (13 MPa) semicrystalline polymers as they exhibited a glass transition temperature (Tg) at -38 °C, melting temperature (Tm) at 46 °C and crystallinity close to 35.9% as determined by DSC. In agreement with this, X-ray diffraction showed reflections at 21.3° and 23.6° for PCL without reflections for atorvastatin suggesting its presence in amorphous form with higher potential bioavailability. Low content of rigid segments led to highly degradable polymer in acidic, alkaline and oxidative media with an acceptable fibroblast cytotoxicity up to 7 days possibly due to low atorvastatin content.

Synthesis and in vitro evaluation of new ethyl and methyl quinoxaline-7-carboxylate 1,4-di-N-oxide against Entamoeba histolytica.

In our search for new antiamoebic agents, a new series of ethyl and methyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives have been synthesized using the Beirut reaction. All compounds were characterized by spectroscopic techniques and elemental analysis. Antiamoebic activity was evaluated in vitro against Entamoeba histolytica strain HM1:IMSS by the microdilution method, and the structure-activity relationship was analyzed. We found that eleven quinoxaline derivatives showed greater activity than metronidazole and nitazoxanide with IC50 values in the range 1.99-0.35 µM. Compounds T-001 and T-016 shows IC50 values of 1.41 and 1.47 µM, respectively, with a value of selectivity index >60.

Efficacy of Salmonella Bacteriophage S1 Delivered and Released by Alginate Beads in a Chicken Model of Infection.

Modern bacteriophage encapsulation methods based on polymers such as alginate have been developed recently for their use in phage therapy for veterinary purposes. In birds, it has been proven that using this delivery system allows the release of the bacteriophage in the small intestine, the site of infection by Salmonella spp. This work designed an approach for phage therapy using encapsulation by ionotropic gelation of the lytic bacteriophage S1 for Salmonella enterica in 2% w/v alginate beads using 2% w/v calcium chloride as crosslinking agent. This formulation resulted in beads with an average size of 3.73 ± 0.04 mm and an encapsulation efficiency of 70%. In vitro, the beads protected the bacteriophages from pH 3 and released them at higher pH. To confirm that this would protect the bacteriophages from gastrointestinal pH changes, we tested the phage infectivity in vivo assay. Using a model chicken (Gallus gallus domesticus) infected with Salmonella Enteritidis, we confirmed that after 3 h of the beads delivery, infective phages were present in the chicken's duodenal and caecal sections. This study demonstrates that our phage formulation is an effective system for release and delivery of bacteriophage S1 against Salmonella Enteritidis with potential use in the poultry sector.