Jesus Gracia-Mora

Solubility, 1H-NMR, and Molecular Mechanics of Mebendazole with Different Cyclodextrins

The solubility behavior and binding constants (Kass) of mebendazole with alpha-, beta-, gamma-, and hydroxypropyl-beta-cyclodextrins (HP-beta-CD) have been investigated in simulated intestinal juice by the Higuchi and Connors method. AL diagrams have been obtained. The equilibrium has also been studied in simulated gastric fluid with HP-beta-CD. The phase solubility, 1H-NMR, and molecular mechanics studies revealed the formation of a 1:1 complex.

Molecular Interactions and Thermodynamic Aspects of the Complexation Reaction between Gentian Violet and Several Cyclodextrins

The complexation process between gentian violet (CV+) and four different cyclodextrins (α-, β-, γ-, and HP-β-CDs) has been investigated under different reaction conditions (pH, solvent, and temperature) by electronic absorption and 1H NMR (NOE and NOESY) spectroscopies. All the binding constants were determined by the direct spectroscopic method. The ΔH and ΔS complexation values have been evaluated and discussed according to the diverse factors that affect the chemical interactions in these systems. A simple association takes place between the secondary hydroxyl or the hydroxypropyl groups of α and HP-β-cycloamyloses, respectively, with the amine group of the gentian violet, while the binding between CV+ and β- or γ-CDs corresponds to a real inclusion. Also, a CV22+ dimmeric species within the γ-CD cavity was detected in aqueous solution, while two molecules of α-CD react with one molecule of gentian violet in DMSO at 294 K. In all the reaction media the β-CD forms 1 : 1 complexes, but in the buffered aqueous solution at pH 7.5 the inclusion is deeper than in the other solvents. It is important to point out that the solvophobic effect is the most important binding factor in the complexation of the CV+ with the α- and HP-β-CDs, while the complexes with β-, and γ-cyclodextrins are mainly stabilized by van der Waals interactions between the guest and the host cavity. In all cases, the inclusion orientation is probably determined by the ion-dipole interactions between gentian violet and the solvent.

Thermodynamic Study of Cyclodextrins Complexation with Benzimidazolic Antihelmintics in Different Reaction Media

The main purpose of this work was to accomplish a comparative study about cyclodextrins complexation equilibria with three benzimidazolic antihelmintics: albendazole (Alb), mebendazole (Meb) and thiabendazole (Thiab). The complexation process with four different cyclodextrins (alpha-, beta-, gamma-, and HP-beta-CDs) was investigated under various temperatures and different reaction media (aqueous solution buffered at pH 7.5, dimethylsulfoxide (DMSO) and DMSO/water at 25/75, 50/50, 75/50 (w/w) mixtures). It was studied by electronic absorption and 1H NMR (NOESY) spectroscopy. Binding constants were determined by electronic absorption spectroscopic method, the DeltaH and DeltaS complexation values were evaluated and discussed according to the diverse factors that affect the chemical interactions in these systems. Solubility has also been determined by the Higuchi and Connors method. In general, albendazole and mebendazole exhibit similar complexation behavior, while thiabendazole acts differently. Classic and non-classic solvophobic effects are mainly the driving and stabilizing forces for complex formation, with the exception in some Thiab-CDs interactions. In all cases, DMSO, an aprotic solvent, should be considered as an active component of the reaction systems.

Fasciola hepatica proteolytic activity in liver revealed by in situ zymography

Fasciola hepatica secretes cysteine proteases that play a role in facilitating parasite migration. The aim of this study was to detect the inhibition of the proteolytic activity of F. hepatica cysteine proteases in the liver of C57BL/6 cathepsin B knockout mice (cat B−/−) and wild-type controls (cat B+/+) by intraperitoneal administration of N-[ N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl]-agmatine, (E-64) using the film in situ zymography (FIZ) technique and image analysis. The FIZ technique revealed that intraperitoneal administration of E-64 dramatically reduced (85%) F. hepatica proteolytic activity in the liver of experimentally infected mice with no discernable side effects. These results suggest the usefulness of the FIZ for determining in vivo activity of F. hepatica proteases, as well as their inhibition by intraperitoneal administration of E-64 in hepatic tissue of infected mice.

Spectroscopic studies of the nickel-substituted Desulfovibrio vulgaris Hildenborough rubredoxin: implication for the nickel site in hydrogenases

An Ni-substituted rubredoxin has been prepared using a new method of metal replacement. The Ni center appears to be constituted by one nickel atom coordinated to four cysteine residues in a distorted tetrahedral geometry. After oxidation, this site gives EPR signals very close to those observed in the Ni-containing hydrogenases. The amino-acid sequences which appear to be involved in the nickel fixation of the substituted rubredoxin show homologies with cysteine-containing motiefs present in the Ni hydrogenase sequences. The different results and observations reported herein are discussed and allow a model to be proposed for nickel coordination in hydrogenases.

Characterization of hybrid microparticles/Montmorillonite composite with raspberry-like morphology for Atorvastatin controlled release

In this work, we prepared a novel composite based on hybrid gelatin carriers and montmorillonite clay (MMT) to analyze its viability as controlled drug delivery system. The objective of this research involves the characterization of composites formed by structured lipid-gelatin micro-particles (MP) and MMT clay. This analysis included the evaluation of the composite according to its rheological properties, morphology (SEM), particle size, XRD, FT-IR, and in vitro drug release. The effect of pH in the properties of the composite is evaluated. A novel raspberry-like or armor MP/MMT clay composite is reported, in which the pH has an important effect on the final structure of the composite for ad-hoc drug delivery systems. For pH values below the isoelectric point, we obtained defined morphologies with entrapment efficiencies up to 67%. The pH level controls the MP/MMT composite release mechanism, restringing drug release in the stomach-like environment. Intended for oral administration, these results evidence that the MP/MMT composite represents an attractive alternative for intestinal-colonic controlled drug delivery systems.

Closantel nano-encapsulated polyvinyl alcohol (PVA) solutions

Abstract The influence of closantel on the rheological and physicochemical properties (particle size and by UV–Vis absorption spectroscopy) of PVA aqueous solutions is studied here. About 1% PVA aqueous solutions were prepared by varying the closantel content. The increase of closantel content led to a reduction in the particle size of final solutions. All the solutions were buffered at pH 7.4 and exhibited shear-thinning behavior. Furthermore, in oscillatory flow, a “solid-like” type behavior was observed for the sample containing 30 μg/mL closantel. Indicating a strong interaction between the dispersed and continuous phases and evidencing an interconnected network between the nanoparticle and PVA, this sample also showed the highest shear viscosity and higher shear thinning slope, indicating a more intrincate structure disrupted by shear. In conclusion, PVA interacts with closantel in aqueous solution and the critical concentration for closantel encapsulation by PVA was about 30 μg/mL; above this concentration, the average particle size decreased notoriously which was associated to closantel interacting with the surface of the PVA aggregates and thus avoiding to some extent direct polymer–polymer interaction.