References of "Evrard, Brigitte"
     in
Bookmark and Share    
Peer Reviewed
See detailSTUDY OF PEGYLATED LIPOSOMES CRYOPROTECTION IN TERMS OF RETENTION EFFICIENCY
Ducat, Emilie ULg; Evrard, Brigitte ULg; Piel, Géraldine ULg

Poster (2008)

Purpose: Print 3G, a peptidic antagonist of oncoproteins involved in breast cancer, was encapsulated in PEGylated liposomes. Seeing its temperature instability, this peptide must be stored at – 20°C. In ... [more ▼]

Purpose: Print 3G, a peptidic antagonist of oncoproteins involved in breast cancer, was encapsulated in PEGylated liposomes. Seeing its temperature instability, this peptide must be stored at – 20°C. In this study, the cryoprotection of PEGylated liposomes was investigated to ensure their stability in terms of size and retention capacity when frozen. Calcein, a self-quenching fluorescent marker encapsulated in liposomes, was used as a tracer of liposome integrity. The release of calcein was studied before and after freezing, with or without cryoprotectants at several concentrations. Methods: Unilamellar vesicles made of SPC:CHOL:mPEG-750-DSPE (47:47:6) or SPC:CHOL:mPEG-2000-DSPE (47:47:6) were prepared by the film evaporation method. Size of the liposomes dispersions containing a cryoprotectant (sucrose, trehalose or lysine) at various concentrations were measured by photon correlation spectroscopy before and after freezing. From these results, two cryoprotectants (at the best molar ratio of sugar-to-lipid) were chosen for future experiments with calcein. Its release from the inner cavity of liposomes was measured fluorometrically before and after freezing, with or without cryoprotectant. The percentage of calcein retained was determined at excitation and emission wavelengths of 490 and 520 nm, respectively. The liposomes were prepared with cryoprotectant either only outside the vesicles or both inside and outside. Results: In regards to the results obtained with PCS, sucrose and trehalose (molar ratio of sugar-to-lipid = 4) were selected for calcein experiments. The best results in terms of retention efficiency were obtained using cryoprotectant inside and outside the vesicles. Liposomes containing mPEG-750-DSPE show the best retention efficiency after freezing with trehalose (75.42 ± 2.39 %, n=3) in comparison with sucrose (62.16 ± 4.34 %, n=3). Liposomes containing mPEG-2000-DSPE doesn’t show significant difference (T-Test) between trehalose (84.27 ± 5.05%, n=3) and sucrose (83.38 ± 3.18 %, n=3). In the future experiments, these results will be compared with experiments of frozen liposomes encapsulating Print 3G. Acknowledgements: This work was supported by the Ministry of the Walloon Region. [less ▲]

Detailed reference viewed: 45 (3 ULg)
Full Text
See detailDEVELOPMENT OF AN INTRAPERITONEAL IMPLANT FOR THE ENDOMETRIOSIS TREATMENT
Krier, Fabrice ULg; Nizet, Dominique; Riva, Raphaël ULg et al

Poster (2008)

Detailed reference viewed: 35 (11 ULg)
Full Text
Peer Reviewed
See detailPreliminary Clinical Assessment of a Gentamicin-Loaded Monoolein Gel Intended to Treat Chronic Osteomyelitis
Ouédraogo, M; Da, C.S; Nacoulma, I.S et al

in Trends in Medical Research (2008), 3(2), 82-89

The aim of this current study was to perform a preliminary clinical assessment of efficacy and safety of a biodegradable gentamicin-loaded monoolein gel. An open single dose, one treatment study including ... [more ▼]

The aim of this current study was to perform a preliminary clinical assessment of efficacy and safety of a biodegradable gentamicin-loaded monoolein gel. An open single dose, one treatment study including 19 patients with chronic osteomyelitis caused by a microorganism sensitive to gentamicin was conducted. After surgical curettage of the infected bone, the dead space was filled in with the gentamicin-loaded monoolein gel. To prevent post-operative septicaemia, a systemic antibiotherapy was prescribed for 3 days following the operation. Clinical, biological and radiological follow-up was performed to assess the efficacy and the safety of the treatment. After a follow-up period ranging from 2 to 12 months, all 19 patients included in the study felt well. Eighteen patients recovered from chronic osteomyelitis without adverse events. The wound of one patient whose bone was exposed did not scar over after 10 months. However, it was no longer infected. In conclusion, gentamicin-loaded monoolein gel was efficacious in treating chronic osteomyelitis without side-effects. [less ▲]

Detailed reference viewed: 35 (3 ULg)
Full Text
Peer Reviewed
See detailIn vitro Biocompatibility and Genotoxicity Assessment of a Gentamicin-Loaded Monoolein Gel Intended to Treat of Chronic Osteomyelitis
Ouédraogo, M; Nacoulma, E.C; Semdé, R et al

in Journal of Pharmacology & Toxicology (2008), 3(5),

The aim of the study was to assess in vitro the biocompatibility and the genotoxicity of a gentamicin-loaded monoolein gel intended to treat of chronic osteomyelitis. Indeed, we are developing ... [more ▼]

The aim of the study was to assess in vitro the biocompatibility and the genotoxicity of a gentamicin-loaded monoolein gel intended to treat of chronic osteomyelitis. Indeed, we are developing biodegradable implants based on monoolein and gentamicin. The results of formulations, physico-chemical characterization of the formulated implants and in vitro release kinetic of gentamicin from implants were encouraging. As biocompatibility and absence of genotoxicity are the prerequisites for safe use of implants, we performed in vitro hemolysis, cytotoxicity and, genotoxicity tests. Hemolysis was evaluated by incubating human erythrocytes in direct contact with the implant whereas cytotoxicity was evaluated by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay using fibroblasts and macrophages. Alkaline comet Assay was used to evaluate genotoxic potential of the implants. From these in vitro assays, the implant based on monoolein and gentamicin showed no genotoxic potential and has satisfactory biocompatibility. [less ▲]

Detailed reference viewed: 28 (1 ULg)
Full Text
Peer Reviewed
See detailIn vivo Biocompatibility and Toxicity Assessment of a Gentamicin-Loaded Monoolein Gel Intended to Treat Chronic Osteomyelitis
Ouédraogo, M; Sanou, M; Ramdé, N et al

in Journal of Pharmacology & Toxicology (2008), 3(5), 386-393

Biocompatibility and preliminary toxicity of a novel gentamicin-loaded monoolein gel (implant) intended for the local treatment of chronic osteomyelitis were investigated in mice. The mice, randomly ... [more ▼]

Biocompatibility and preliminary toxicity of a novel gentamicin-loaded monoolein gel (implant) intended for the local treatment of chronic osteomyelitis were investigated in mice. The mice, randomly allotted in 3 groups of 10, received respectively a single dose (0.05 mL) of normal saline, monoolein and the gel by subplantar injection. Clinical monitoring and assessment of induced oedema were carried out during 52 days after implantation. A histologic examination of the implantation site was performed at the end of the experiment. Renal and hepatic functions of the implant were also assessed on 52 days post-implantation by using biochemical and histological methods. In mice, no adverse reaction occurred after implantation. Only, a transitional foreign body reaction was observed in mice implanted by the monoolein and the implant. The paw volume of the mice increased within 3 h post-implantation and returned to baseline by 52 days. The liver and kidneys histology at light microscopy and biochemical parameters were similar for all mice. Further investigation is undertaken to detect eventual early damages which could have been resolved with time. Nevertheless, the novel gel is biocompatible and doesn`t show sub-chronic toxicity. [less ▲]

Detailed reference viewed: 43 (5 ULg)
Full Text
Peer Reviewed
See detailSynthesis and pharmacological evaluation of a new targeted drug carrier system: β-Cyclodextrin coupled to oxytocin
Bertolla, C; Rolin, S; Evrard, Brigitte ULg et al

in Bioorganic & Medicinal Chemistry Letters (2008), 18

β-Cyclodextrin (β-CD) was monofunctionalized into its carboxylic derivative and then conjugated to the N-side of oxytocin (OT), a nonapeptide involved in human behavior and myometrium contraction. On ... [more ▼]

β-Cyclodextrin (β-CD) was monofunctionalized into its carboxylic derivative and then conjugated to the N-side of oxytocin (OT), a nonapeptide involved in human behavior and myometrium contraction. On isolated rat myometrium, this conjugate (β-CD-OT) partly preserves the contracting activity of OT (EC50 = 0.40 μM vs 1.7 nM). Moreover, the contraction induced frequency is also lowered by β-CD-OT. This novel hydrophilic targeted carrier could form a host–guest complex with prostaglandins and their derivatives used as labor inducers or with anticancer drugs used in cervix and endometrial cancer. This strategy can improve the solubility, the stability, and/or the biological activity of these drugs as well as reducing their side-effects. [less ▲]

Detailed reference viewed: 13 (2 ULg)
Full Text
Peer Reviewed
See detailMonoolein-water liquid crystalline gels of gentamicin as bioresorbable implants for the local treatment of chronic osteomyelitis: in vitro characterization
Ouédraogo, M; Semdé, R; Somé, I.T et al

in Drug Development & Industrial Pharmacy (2008), 34

To maximize the efficacy of chronic osteomyelitis antibiotherapy while reducing antibiotic systemic toxicity, as well as time and costs of hospitalizations, it has been thought that monoolein-water gels ... [more ▼]

To maximize the efficacy of chronic osteomyelitis antibiotherapy while reducing antibiotic systemic toxicity, as well as time and costs of hospitalizations, it has been thought that monoolein-water gels incorporating gentamicin sulfate could be used as local, bioresorbable,and sustained-release implants. For this purpose, four formulations were examined with regard to their physicochemical and in vitro drug release characteristics. Hot stage microscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA),and X-ray diffraction showed cubic liquid crystalline and eutectic structures. The more suitable formulation consisting of 80-15-5%wt/wt monoolein-water-gentamicin sulfate progressively released the antibiotic for a period of 3 weeks without burst effect. Moreover, the content and the release profile of gentamicin sulfate were not significantly changed after storage at 2-6 degrees C for a period of 10 months. [less ▲]

Detailed reference viewed: 19 (1 ULg)
Full Text
Peer Reviewed
See detailA novel formulation of inhaled doxycycline reduces allergen-induced inflammation, hyperresponsiveness and remodeling by matrix metalloproteinases and cytokines modulation in a mouse model of asthma
Guéders, Maud ULg; Bertholet, P.; Perin, Fabienne ULg et al

in Biochemical Pharmacology (2008), 75(2), 514-26

Background In this study, we assess the effectiveness of inhaled doxycycline, a tetracycline antibiotic displaying matrix metalloproteinases (MMP) inhibitory effects to prevent allergen-induced ... [more ▼]

Background In this study, we assess the effectiveness of inhaled doxycycline, a tetracycline antibiotic displaying matrix metalloproteinases (MMP) inhibitory effects to prevent allergen-induced inflammation, hyperresponsiveness and remodeling. MMPs play key roles in the complex cascade of events leading to asthmatic phenotype. Methods Doxycycline was administered by aerosols by the mean of a novel formulation as a complex with hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) used as an excipient. BALB/c mice (n = 16–24 in each group) were sensitized and exposed to aerosolized ovalbumin (OVA) from day 21 to 27 (short-term exposure protocol) or 5 days/odd weeks from day 22 to 96 (long-term exposure protocol). Results In the short-term exposure model, inhaled doxycycline decreased allergen-induced eosinophilic inflammation in bronchoalveolar lavage (BAL) and in peribronchial areas, as well as airway hyperresponsiveness. In lung tissue, exposure to doxycycline via inhaled route induced a fourfold increase in IL-10 levels, a twofold decrease in IL-5, IL-13 levels and diminished MMP-related proteolysis and the proportion of activated MMP-9 as compared to placebo. In the long-term exposure model, inhaled doxycycline significantly decreased the extent of glandular hyperplasia, airway wall thickening, smooth muscle hyperplasia and subepithelial collagen deposition which are well recognized features of airway remodeling. Conclusion Doxycycline administered by aerosols decreases the allergen-induced airway inflammation and hyperresponsiveness and inhibits the development of bronchial remodeling in a mouse model of asthma by modulation of cytokines production and MMP activity. [less ▲]

Detailed reference viewed: 111 (37 ULg)
Peer Reviewed
See detailOptimization of a drug-cyclodextrin complexation reaction by a static supercritical carbon dioxide process
Brion, Michael; Nizet, Dominique; Evrard, Brigitte ULg

Poster (2008)

Detailed reference viewed: 10 (0 ULg)
Full Text
Peer Reviewed
See detailValidation of manufacturing process of Diltiazem HCl tablets by NIR spectrophotometry (NIRS)
Bodson, Cédric; Rozet, Eric ULg; Ziemons, Eric ULg et al

in Journal of Pharmaceutical & Biomedical Analysis (2007), 45(2), 356-361

The goal of this study was to apply the Process Analytical Technology FDA's initiative in pharmaceutical tablets manufacturing. Near Infrared Spectrophotometry (NIRS) was used as a non-destructive, very ... [more ▼]

The goal of this study was to apply the Process Analytical Technology FDA's initiative in pharmaceutical tablets manufacturing. Near Infrared Spectrophotometry (NIRS) was used as a non-destructive, very fast technique requiring no sample preparation. Direct compression powder blends containing Diltiazem HCl as a model drug were pressed into tablets for the calibration and the validation steps. First, a partial least squares model was built to calibrate the NIR spectrometer. Then, this model was validated and compared with a validated UV spectrophotometry reference method. For this comparison, the Bland and Altman's statistical method was applied. The manufacturing process was validated by producing three batches at three different concentration levels. The NIR analysis of these batches was performed during 3 days. This study shows that NIRS can be used to validate the whole manufacturing process and not only as an analytical method for tablets assay. NIRS is an interesting tool to show possible variations during the manufacturing process which could lead the finished product to fall outside of specifications. [less ▲]

Detailed reference viewed: 180 (13 ULg)
Full Text
See detailCYCLODEXTRIN INCLUSIONS COMPLEXES OF PYRIMIDINE-2,4,6-TRIONES
Evrard, Brigitte ULg; Bartsch, Pierre ULg; Endele, Richard et al

Patent (2007)

Detailed reference viewed: 23 (5 ULg)
Full Text
Peer Reviewed
See detailStudy of the relationship between lipid binding properties of cyclodextrins and their effect on the integrity of liposomes
Piel, Géraldine ULg; Piette, Marie ULg; Barillaro, Valery et al

in International Journal of Pharmaceutics (2007), 338(1-2), 35-42

It is well known that cyclodextrins are able to extract lipids constituting membranes, increasing their fluidity and permeability. This behaviour towards biological membranes is directly linked to the ... [more ▼]

It is well known that cyclodextrins are able to extract lipids constituting membranes, increasing their fluidity and permeability. This behaviour towards biological membranes is directly linked to the toxicological effects of methylated cyclodextrins. However, confusion is currently made in the literature between the different methylated cyclodextrin derivatives. Moreover, a new methylated cyclodextrin derivative recently occurred in the market. the Crysmeb (R). We wanted to compare and understand the effect of the most currently used cyclodextrins on a model membrane. We studied the influence of natural cyclodextrins (beta CD and gamma CD), methylated derivatives (2,6-dimethyl-beta CD (Dimeb), 2,3,6-trimethyl-beta CD (Trimeb) and randomly methylated-beta CD (Rameb), as well as the new derivative Crysmeb), hydroxypropylated derivatives (HP beta CD of different substitution degrees and HP gamma CD) and the sulfobutylated derivative (SBE beta CD) on the release of a fluorescent marker encapsulated in the inner cavity of liposomes. It was shown that the observed effect on calcein release can be directly related to the affinity of cyclodextrins for both lipid components of liposomes, cholesterol and phosphatidylcholine. From this relationship, we were able to determine, for each cyclodextrin, a theoretical concentration giving rise to 50% or 100% calcein release. This theoretical concentration was confirmed experimentally. We have also showed that cyclodextrins which provoke calcein release also induce large structure modifications of liposomes. (c) 2007 Elsevier B.V. All rights reserved. [less ▲]

Detailed reference viewed: 38 (11 ULg)