Etude pharmacocinétique d'un nouvel inhibiteur des MMPs (I-col 51) après administration orale et intraveineuse de soultions à base d'hydroxypropyl-b-cyclodextrine

Conference (2005, March)

Solid Lipid Microparticles: Formulation, Preparation, Characterisation, Drug Release and Applications

in Expert Opinion on Drug Delivery (2005), 2(1), 75-87

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 ... [more ▼]

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. A detailed discussion of the characteristics of SLMs follows, and includes the determination of particle size distribution, the determination of SLM morphology, the solid-state analysis, the determination of SLM drug loading and the factors influencing it. The in vitro drug release studies that have been carried out so far and the parameters affecting them are also described. Some preliminary in vivo aspects (in vivo drug release studies, biocompatibility studies and in vivo fate) are also considered. [less ▲]

Study of solid lipid micriparticles as sustained release delivery system for pulmonary administration

Conference (2005)

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

in AAPS Journal (2005), 7(1), 149-155

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 ... [more ▼]

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. Miconazole plasma concentrations were determined by a high-performance liquid chromatography method. Preliminary in vitro dissolution data showed that CPLX exhibits a faster and higher dissolution rate than either PHYS or MICO. Following CPLX oral administration, mean area under the plasma concentration curve (AUC(0-infinity)) for miconazole was 95.0 +/- 55.8 microg/min/mL, with the peak plasma concentration (C(max) 0.59 +/- 0.39 microg/mL) at 19.30 minutes. The AUC(0-infinity) and C(max) values were significantly higher than those after oral administration of PHYS (AUC(0-infinity) 38.5 +/- 12.7 microg/min/mL and C(max) 0.24 +/- 0.08 microg/mL; P < .1) and of MICO (AUC(0-infinity) 24.1 +/- 14.0 microg/min/mL and C(max) 0.1 +/- 0.05 microg/mL; P < .1). There were also significant differences between PHYS and MICO (P < .1). The results of the study indicate that CPLX shows improved dissolution properties and a higher relative oral bioavailability compared with PHYS and MICO. [less ▲]

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

in Journal of Pharmacy & Pharmaceutical Sciences : A Publication of the Canadian Society for Pharmaceutical Sciences (2004), 7(3), 378-388

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 ... [more ▼]

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. RESULTS: The best inclusion yields were achieved with the combination of MICO base and HPgammaCD with or without acids. Maleic and fumaric acids influenced the MICO inclusion differently in function of their conformation. During the process, a miconazole salt was observed with maleic acid and characterized by thermal analysis and mass spectrometry. The kinetics inclusion followed a saturation-type shape curve. FT-IR confirmed the presence of genuine inclusion complexes. The complexes MICO base/HPgammaCD/(L-tartaric acid) enhanced the dissolution rates of MICO more than the corresponding physical mixtures did. Lastly, the stability study revealed that the complexes were stable. CONCLUSIONS: The formation of stable complexes between MICO and CDs is possible using SCCO(2). Moreover an acidic ternary compound is able to modify the formation of the complex. The inclusion complexes, which show better dissolution profiles than those with the corresponding physical mixtures, could lead to an increase of the oral bioavailability of MICO. [less ▲]

Modulation of the arachidonic cascade with omega 3 fatty acids or analogues: Potential therapeutic benefits

in Mini-Reviews in Medicinal Chemistry (2004), 4(6), 659-668

Increasing interest in the role of omega 3 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 ... [more ▼]

Increasing interest in the role of omega 3 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 w3 fatty acids intake as well as its interest in the prevention or treatment of the above-mentioned pathologies. [less ▲]

Effect of methylated-b-cyclodextrin on the skin and influence on cyproterone acetate percutaneous absorption

Poster (2004, May)

Etude des interactions cyclodextrines-liposomes: modification de la cinétique de libération de l'inuline encapsulée dans des lioposomes bioadhésifs en présence de méthyl-b-cyclodextrine

Conference (2004, January)

Solid lipid Nanoparticles for administration by inhalation : Optimisation of manufacturing parameters and preliminary tolerance study

Conference (2004)

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

in Antimicrobial Agents and Chemotherapy (2004), 48(11), 4342-4348

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 ... [more ▼]

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. We found that a bioadhesive polycarbophil gel (Noveon) at pH 5.5 is able to maintain the bioactivity of GM-CSF at 4 or 37°C for at least 7 days, whereas a decreased activity of GM-CSF was observed when the molecule is included in other polymer gels. GM-CSF incorporated in the polycarbophil gel was also a potent factor in enhancing the colonization of DC into organotypic cultures of HPV-transformed keratinocytes since the infiltration of DC in the in vitro-formed (pre)neoplastic epithelium was very low under basal conditions and dramatically increased in the presence of GM-CSF gel. We next demonstrated that GM-CSF incorporated in polycarbophil gel induces the recruitment of human DC in a human (pre)neoplastic epithelium grafted into NOD/SCID mice. The efficacy of GM-CSF in this formulation was equivalent to that observed with liquid GM-CSF. These results suggest that GM-CSF incorporated in polycarbophil gel could play an important role in the recruitment of DC/LC in mucosal surfaces and be useful as a new immunotherapeutic approach for genital HPV-associated (pre)neoplastic lesions. [less ▲]