Pharmacokinetic study of a new synthetic MMP inhibitor (Ro 28-2653) after IV and oral administration of cyclodextrin solutions.

Ro 28-2653 (5-biphenyl-4-yl-5-[4-(4-nitro-phenyl)-piperazin-1-yl]-pyrimidine-2,4,6-trione) is a new synthetic inhibitor of matrix metalloproteinases (MMPs) with a high selectivity towards MMP2, MMP9 and membrane type 1-MMP. It has been shown that cyclodextrins (CDs) are able to form inclusion complexes with Ro 28-2653 and to increase its aqueous solubility. The aim of this study is to demonstrate that an increase in Ro 28-2653 solubility, via ternary complex formation, can lead to an increase in the oral bioavailability of this drug.

Betamethasone-in-cyclodextrin-in-liposome: the effect of cyclodextrins on encapsulation efficiency and release kinetics.

Lipophilic drugs have limited solubility in phospholipid systems, hence maximum entrapment levels in liposomes are known to be low. "Drugs-in-cyclodextrin-in-liposome" systems were previously proposed to overcome this drawback but studies were limited to betaCD and HPbetaCD. In some cases, other cyclodextrins may be more interesting than betaCD or HPbetaCD, such as methylated cyclodextrins.

Solid lipid microparticles: formulation, preparation, characterisation, drug release and applications.

This review details the properties of solid lipid microparticles (SLMs): a promising drug carrier system that has been until now rather unexploited. First, the advantages of SLMs compared with other drug carrier systems are listed. Then an overview of SLM manufacturing compounds and techniques is presented.

[Evaluation of rapid, semi-quantitative assay of C-reactive protein in whole blood, Actim CRP].

We evaluated a rapid and semi-quantitative C-Reactive Protein test on whole blood, the Actim CRP (Fumouze). Based on immuno-chromatography technology, this test ranked the blood sample in four groups: < 10 mg/L, 10-40 mg/L, 40-80 mg/L and > 80 mg/L. This evaluation finds an excellent repeatability, the absence of hook-effect for high levels of CRP and an independence from classical biological interferences: haemolysis, turbidity and bilirubin.

Inhaled fluticasone reduces bronchial responsiveness and airway inflammation in cats with mild chronic bronchitis.

This study investigated the effect of inhaled fluticasone on lower airway inflammation and bronchial responsiveness (BR) to inhaled carbachol in cats with very mild, chronic bronchitis (n = 5) that were compared with healthy cats serving as controls (n = 6). Chest radiographs, BR tests performed non-invasively by barometric whole body plethysmography (BWBP) and bronchoalveolar lavage (BAL) were performed before and after treatment. BR was quantified by calculating the concentration of carbachol inducing bronchoconstriction (C-Penh300%), defined as a 300% increase of baseline Penh, an index of bronchoconstriction obtained by BWBP.

Oral bioavailability in pigs of a miconazole/hydroxypropyl-gamma-cyclodextrin/L-tartaric acid inclusion complex produced by supercritical carbon dioxide processing.

The objective of this study was to determine the pharmacokinetic parameters of miconazole after oral administration of a miconazole/hydroxypropyl-gamma-cyclodextrin(HPgammaCD)/L-tartaric acid inclusion complex produced by supercritical carbon dioxide processing. The pharmacokinetics of the miconazole ternary complex (CPLX), of the corresponding physical mixture (PHYS), and of miconazole alone (MICO) were compared after oral administration. Six mixed-breed pigs received each formulation as a single dose (10 mg miconazole/kg) in a crossover design.

The effect of cyclodextrins on the aqueous solubility of a new MMP inhibitor: phase solubility, 1 H-NMR spectroscopy and molecular modeling studies, preparation and stability study of nebulizable solutions.

Purpose: Ro 28-2653 (RO) is a synthetic inhibitor of matrix metalloproteinases (MMPs), which is potentially effective against bronchial remodeling. Given that this molecule has very poor aqueous solubility, different cyclodextrins (CDs) have been tested to increase its solubility. The aim of this study was to prepare and to characterize inclusion complexes between RO and CDs, in order to develop nebulizable solutions.

Preparation and in vivo toxicity study of solid lipid microparticles as carrier for pulmonary administration.

The purpose of this research was to investigate the effects of processing conditions on the characteristics of solid lipid microparticles (SLM) with a potential application as carriers for pulmonary administration. Compritol (5.0% wt/wt) SLM dispersions were prepared by rotor-stator homogenization, at different surfactant concentrations and emulsification times.

[Prophylactic antibiotic therapy (amoxicillin + clavulanic acid) before embryo transfer for IVF is useless. Results of a randomized study].

Objectives: We studied the implantation rate during IVF cycles according to the prescription or not of antibiotics.

Materials And Methods: During a 5-month period all the patients aged less than 38 years were randomized into two groups according to an independent personal variable. In group 1 amoxicilline + clavulanic acid 1g/125 mg were administrated from the ovum pick-up day for 6 days.

Automated method for the determination of a new matrix metalloproteinase inhibitor in ovine plasma and serum by coupling of restricted access material for on-line sample clean-up to liquid chromatography.

A fully automated liquid chromatographic method was developed for the determination of Ro 28-2653, a new synthetic inhibitor of matrix metalloproteinases (MMPs), in ovine serum and plasma. The method was based on the coupling of a pre-column packed with restricted access material, namely LiChrospher RP-8 ADS (alkyl diol silica), for sample clean-up to an analytical column containing octyl silica stationary phase. One hundred microl of biological sample, to which 2-propanol was automatically added, were injected onto the ADS pre-column, which was then washed with a washing liquid consisting of a mixture of 25 mM phosphate buffer (pH 7.

Effect of acidic ternary compounds on the formation of miconazole/cyclodextrin inclusion complexes by means of supercritical carbon dioxide.

Purpose: The aim of the study is to evaluate the effect of different acidic compounds on the inclusion of miconazole (MICO) in several cyclodextrins (CDs) using supercritical carbon dioxide (SCCO(2) ) processing.

Methods: Physical mixtures were processed by SCCO(2) at 30 MPa, 125 degrees C during 60 minutes in a static mode to produce inclusion complexes. The inclusion complexes were characterized by differential solubility, Fourier transform infrared spectroscopy (FT-IR) and dissolution test.

Delivery of granulocyte-macrophage colony-stimulating factor in bioadhesive hydrogel stimulates migration of dendritic cells in models of human papillomavirus-associated (pre)neoplastic epithelial lesions.

Because of the central role of dendritic cells and/or Langerhans cells(DC/LC) in the induction of cellular immune responses, pharmacological agents that modulate the recruitment of these cells might have a clinical interest. The present study was designed to evaluate the capacity of several pharmaceutical formulations to topically deliver granulocyte-macrophage colony-stimulating factor (GM-CSF) on human papillomavirus (HPV)-associated genital (pre)neoplastic lesions. The formulations were evaluated for their bioactivity and for their potential to recruit DC in organotypic cultures of HPV-transformed keratinocytes.

Development and validation of a high-performance liquid chromatographic method for the determination of cyproterone acetate in human skin.

In the framework of a preliminary study on the transdermal penetration of cyproterone acetate (CPA), a simple and rapid procedure involving an extraction step coupled to a HPLC-UV determination has been developed for the separation and quantification of CPA in the two main skin layers-epidermis and dermis-after local application. The separation of epidermis and dermis layers was carefully carried out by means of a sharp spatula after skin immersion in heated water at 65 degrees C. The two skin layers were then treated separately according to the same process: (1) sample homogenization by vibration after freezing with liquid nitrogen in a Mikro-Dismembrator; (2) CPA extraction with methanol after addition of the internal standard (betamethasone dipropionate); (3) centrifugation; (4) evaporation of a supernatant aliquot; (5) dissolution of the dry residue in methanol and addition of water; (6) centrifugation; (7) injection of a supernatant aliquot into the HPLC system.

Modulation of the arachidonic cascade with omega3 fatty acids or analogues: potential therapeutic benefits.

Increasing interest in the role of omega3 fatty acids has arisen in these latest years since evidence of their implication in the cardioprotective fish based diet of the Inuit has been demonstrated. Furthermore, several in vitro, in vivo and epidemiological studies support the benefit of this fatty acids intake in various pathological states such as in the cardiovascular, cancer, inflammation, psychiatric, paediatric, pulmonary, dermatological and ophthalmologic fields. This review will focus on metabolism and pharmacological implication of omega3 fatty acids intake as well as its interest in the prevention or treatment of the above-mentioned pathologies.

Electronic and photophysical properties of a novel phenol bound dinuclear ruthenium complex: evidence for a luminescent mixed valence state.

A novel dinuclear ruthenium(II) complex bridged by dianionic bridge 3-(2-phenol)-5-(pyridin-2-yl)-1,2,4-triazole in which the ruthenium metal atoms are bound through N,N coordination to the pyridine and triazole and O,N coordination to the triazole and phenolate is described. The electrochemical, spectroscopic and photophysical behaviour of the dimer is compared with its associated N,N- and O,N-coordinated mononuclear complexes. The mixed valence complex was prepared electrochemically and a weak inter-valence charge transfer transition is observed which from Hush theory provides an electronic coupling matrix element of 666 cm(-1), suggesting the complex is weakly coupled and valence trapped.

Cyclodextrins as a potential carrier in drug nebulization.

The inhalation route is widely studied for many drug applications focusing on either local or systemic distributions. One matter of concern is the solubilization of hydrophobic drugs. We have studied the feasibility of using different cyclodextrins (CDs) to elaborate pharmaceutical formulations for the inhalation route and tested the short-term toxicity of such formulations administered by inhalation to C57BL/6 mice.

Skin compatibility of cyclodextrins and their derivatives: a comparative assessment using a corneoxenometry bioassay.

Few studies have been performed to assess the risk of skin damage by cyclodextrins (CD) and they have yielded contradictory results. The present study was conducted using the corneoxenometry bioassay on human stratum corneum to compare the skin compatibility of CD currently used in pharmaceutical preparations (betaCD, gammaCD, Rameb, Dimeb, Trimeb, HP-betaCD and HP-gammaCD) and that of new amphiphilic CD derivatives, namely, the phospholipidyl-CD (DMPE-Dimeb and DMPE-Trimeb). All the tested CD were well tolerated by the stratum corneum at a concentration of 5%.

Pathogenic role of matrix metalloproteases and their inhibitors in asthma and chronic obstructive pulmonary disease and therapeutic relevance of matrix metalloproteases inhibitors.

Matrix metalloproteinases (MMPs) are an at least 23 member family of calcium and zinc dependent enzymes implicated in many physiological and pathological processes. Asthma, chronic obstructive pulmonary disease (COPD) and emphysema are diseases associated with an inflammation of the airways and lung parenchyma. In this review, we focus on the role played by MMPs in the pathogenesis of inflammation, airway remodelling and alveolar destruction, depicting the observational studies in humans and the experimental studies in animal models.

Involvement of semenogelin-derived peptides in the antibacterial activity of human seminal plasma.

Mechanisms for protecting spermatozoa, and the testes that produce them, from infection are essential, given the importance of these cells and organs for the fertility of the individual and perpetuation of the species. This is borne out by the publication of numerous papers on this subject over the last 50 years. We extended our work and that of others on the anti-infectious defense system of the male genital tract, using a new strategy for the direct identification of antibacterial molecules in human seminal plasma.

Systematic characterization of oil-in-water emulsions for formulation design.

Oil-in-water emulsions varying in surfactant concentration and manufacturing process were prepared. About 10 experiments were performed to characterize them. The goal of this research was to find out which tests should systematically be carried out to assess efficiently the stability and the properties of an emulsified preparation.

New insights into the rat spermatogonial proteome: identification of 156 additional proteins.

Despite the essential role played by spermatogonia in testicular function, little is known about these cells. To improve our understanding of their biology, our group recently identified a set of 53 spermatogonial proteins using two-dimensional (2-D) gel electrophoresis and mass spectrometry. To continue this work, we investigated a subset of the spermatogonial proteome using narrow range immobilized pH gradients to favor the detection of less abundant proteins.

Expression of antimicrobial defensins in the male reproductive tract of rats, mice, and humans.

Defensins are antimicrobial peptides that play a major role in innate immunity. Using reverse transcriptase-polymerase chain reaction, immunochemistry, or both, we performed a search of all presently known defensins in rat testis, epididymis, and isolated testicular cells; in mouse testis and epididymis; and in human testis and ejaculates. In the rat, all alpha- and beta-defensins except RNP-4 were expressed within the testis, whereas alpha-defensins RNP1-2, RNP-4, and beta-defensins RBD-1 and RBD-2 were present within the epididymis.

Oral bioavailability in sheep of albendazole from a suspension and from a solution containing hydroxypropyl-beta-cyclodextrin.

Albendazole (ABZ) is a benzimidazole derivative with a broad spectrum of activity against human and animal helminthe parasites. ABZ has a very poor aqueous solubility. This study shows that hydroxypropyl-beta-cyclodextrin (HP-beta-CD) is able to form inclusion complexes with ABZ and that is able to increase its aqueous solubility.

Determination of the free/included piroxicam ratio in cyclodextrin complexes: comparison between UV spectrophotometry and differential scanning calorimetry.

Few analytical techniques allow to evaluate the inclusion yield of cyclodextrin-drug complexes, because most manufacturing processes give amorphous products. In this study, we have developed an alternative method to differential scanning calorimetry, to accurately determine the free/complexed piroxicam ratio by UV spectroscopy. This method is based on the differential solubility of the piroxicam-beta-cyclodextrin 1:2.

Proteome analysis of rat spermatogonia: reinvestigation of stathmin spatio-temporal expression within the testis.

Stathmin is a protein known to be involved in various cell processes including cell proliferation and differentiation. It has already been described in the testis but its recent identification using a proteomic approach in mitotic spermatogenetic stem cells named spermatogonia (Guillaume et al., 2000) has lead us to reinvestigate its expression within the testis.