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Papers by Claudie Bourgaux

Research paper thumbnail of Self-Assembly of Squalene-Based Nucleolipids: Relating the Chemical Structure of the Bioconjugates to the Architecture of the Nanoparticles

Research paper thumbnail of EJOC Cover

Research paper thumbnail of Influence of the nanoprecipitation conditions on the supramolecular structure of squalenoyled nanoparticles

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Jan 22, 2015

Hydrophobic organic compounds dissolved in a polar solvent can self-assemble into nanoparticles (... more Hydrophobic organic compounds dissolved in a polar solvent can self-assemble into nanoparticles (NPs) upon nanoprecipitation into water. In the present study, we have investigated the structure of squalenacetyl-adenosine (SQAc-Ad) nanoparticles which were previously found to exhibit impressive neuroprotective activity. When obtained by nanoprecipitation of a SQAc-Ad ethanolic solution into water, two different supramolecular organizations of SQAc-Ad NPs were evidenced, depending on the water-to-ethanol volume ratio. It has been shown that a fraction of the solvent remained associated with the NPs, despite prolonged evaporation under reduced pressure after nanoprecipitation, and that this residual solvent dramatically affected their structure. This study points to the importance of being in the "Ouzo" region to minimize the amount and effect of residual solvent and to control the structure of NPs.

Research paper thumbnail of Novel self assembling nanoparticles for the oral administration of fondaparinux: Synthesis, characterization and in vivo evaluation

Journal of Controlled Release

Fondaparinux (Fpx) is the anticoagulant of choice in the treatment of short- and medium-term thro... more Fondaparinux (Fpx) is the anticoagulant of choice in the treatment of short- and medium-term thromboembolic disease. To overcome the low oral bioavailability of Fpx, a new nanoparticulate carrier has been developed. The nanoparticles (NPs) contain squalenyl derivatives, known for their excellent oral bioavailability. They spontaneously self-assemble upon both electrostatic and hydrophobic interactions between the polyanionic Fpx and cationic squalenyl (CSq) derivatives. The preparation conditions were optimized to obtain monodisperse, stable NPs with a mean diameter in the range of 150-200nm. The encapsulation efficiencies were around 80%. Fpx loadings reached 39wt.%. According to structural and morphological analysis, Fpx and CSq organized in spherical multilamellar ("onion-type") nanoparticles. Furthermore, in vivo studies in rats suggested that Fpx was well absorbed from the orally administered NPs, which totally dissociated when reaching the blood stream, leading to th...

Research paper thumbnail of Nanostructures and polymorphisms in protein stabilised lipid nanoparticles, as food bioactive carriers: contribution of particle size and adsorbed materials

Procedia Food Science, 2011

Research paper thumbnail of Surface modified Mg-doped ZnO QDs for biological imaging

European Journal of Nanomedicine, 2015

Research paper thumbnail of Structural and thermal characterization of glyceryl behenate by X-ray diffraction coupled to differential calorimetry and infrared spectroscopy

International journal of pharmaceutics, Jan 24, 2007

Physical and thermal properties of glyceryl behenate (Compritol 888 ATO) used as sustained-releas... more Physical and thermal properties of glyceryl behenate (Compritol 888 ATO) used as sustained-release matrix in pharmaceutical applications are studied by coupled time-resolved synchrotron X-ray diffraction and Differential Scanning Calorimetry combined with Infrared Spectroscopy. With these techniques, all polymorphs formed in glyceryl behenate, analyzed as received and after various thermal treatments from quenching to slow crystallization, are characterized. By using different well-controlled mixtures of mono-, di- and tribehenate, we identify each lamellar phase observed in the glyceryl behenate. Finally the influence of the crystallization rate on the formation of preferential conformations was also analyzed in order to bring insights into the polymorphism of glyceryl behenate. By changing the crystallization rate of the sample, it was shown that one can favor the formation of preferential polymorphs in the sample. In particular the crystallization at 10 degrees C/min seems to be ...

Research paper thumbnail of Unsaturated fatty acid enriched vs. control milk triacylglycerols: Solid and liquid TAG phases examined by synchrotron radiation X-ray diffraction coupled with DSC

Food Research International, 2015

ABSTRACT The fatty acid composition of milk triacylglycerols (TAGs) can be modified to improve th... more ABSTRACT The fatty acid composition of milk triacylglycerols (TAGs) can be modified to improve their nutritional properties and the long-term health of consumers. However, the consequences of an increase in unsaturated fatty acid (UFA) content on the physical properties of milk TAGs remain to be elucidated. This study aimed at comparing the crystallisation properties and melting behaviour of control vs. UFA-enriched milk TAGs using the coupling of time-resolved synchrotron X-ray diffraction and differential scanning calorimetry on cooling and then heating at 3 °C/min. On cooling from the melt, high crystallisation temperature (HCT) TAGs solidify from 15.8 °C in α 2L (45–49 Å) structures, then low crystallisation temperature (LCT) TAGs form α 3L structures with a higher thickness (75.5 Å vs. 71.5 Å) and a delay (8.5 °C vs. 12.1 °C) for UFA-enriched TAG. On heating, melting of TAGs crystals and formation of 3L2 (64.7–80.1 Å) and β′ 2Lf (40–44 Å) crystals associated with polymorphic reorganisations have been characterised. The organisation of TAG molecules in their liquid state revealed a higher thickness for UFA-enriched TAGs as compared to control TAGs. Such results improve the knowledge about the mechanisms of TAG crystallisation as a function of their FA composition and are important for the technological utilisation of UFA-enriched TAGs in food products.

Research paper thumbnail of Lipidic spherulites as magnetic resonance imaging contrast agents

New J. Chem., 2014

ABSTRACT Magnetic resonance imaging is an excellent technique to achieve anatomical details and h... more ABSTRACT Magnetic resonance imaging is an excellent technique to achieve anatomical details and highly resolved images. The search for efficient contrast agents to increase the signal to background ratio led us to evaluate paramagnetic spherulites as potential Magnetic Resonance Imaging (MRI) contrast agents. Spherulites are supramolecular assemblies, made of lipidic concentric multilayers, able to encapsulate with high efficiency soluble macromolecules. Despite their highly interesting structure, spherulites have never been proposed as imaging agents. We proposed here three approaches to render spherulites paramagnetic: encapsulating a soluble contrastophore, inserting a lipidic contrastophore derivative or grafting a soluble contrastophore at the surface of the spherulites. Following similar strategies, liposomes were prepared for comparison. The conservation of the spherulite structure, throughout these three strategies, was shown by cryoelectron microscopy and small angle light scattering. The effect of the paramagnetic spherulites was studied by magnetic resonance imaging at different magnetic fields. The results showed that insertion of a contrastophore lipidic derivative into spherulite bilayers and grafting a contrastophore at the surface of the spherulites were the two strategies which led to the highest MRI contrast improvement.

Research paper thumbnail of Liposomal formulation of a glycerolipidic prodrug for lymphatic delivery of didanosine via oral route

Didanosine is a polar drug with poor membrane absorption and high hepatic first pass metabolism. ... more Didanosine is a polar drug with poor membrane absorption and high hepatic first pass metabolism. This study aimed at developing a lipidic formulation of a glycerolipidic prodrug of didanosine in order to improve its bioavailability. In the course of a preformulation study, the glycerolipidic prodrug of didanosine was characterized by microscopy, DSC and XRDT. In anhydrous conditions, the prodrug displayed a polymorphic behaviour similar to that of triglycerides. Then, we evaluated three types of lipidic formulations (emulsions, mixed micelles and liposomes) in order to encapsulate the prodrug. Solubilities in water - even in the presence of taurocholate micelles - but also in some oils were very low (max 244 microg/mL) as the prodrug was found to be amphiphilic (log P=2). On the contrary, the prodrug was found to be perfectly incorporated in dipalmitoylphosphatidylcholine (DPPC) multilamellar liposomes up to a ratio of 1:5 (mol:mol) prodrug:DPPC as suggested by HPLC-UV and DSC experiments. Moreover, these liposomes could be freeze-dried whereas the chemical integrity of the prodrug was preserved. Then, the freeze-dried liposomal preparation could be formulated as gastro-resistant capsules to prevent didanosine from acidic degradation. Further experiments are on the way to evaluate in vitro the absorption of prodrug incorporated in liposomes by enterocytes.

Research paper thumbnail of Interactions of anticancer drugs with biomembranes: What can we learn from model membranes?

The interactions of anticancer drugs with cell membranes are of primary importance for drug trans... more The interactions of anticancer drugs with cell membranes are of primary importance for drug transport, accumulation and activity. However, these interactions are very difficult to investigate because of the complexity of biological membranes. Lipid model membranes have therefore been built to gain insight into the collective role of lipids in drug-membrane interactions. Membranes can act as a barrier for drug molecules, sequester them or conversely may allow them to freely diffuse, thereby modulating the accumulation of drugs into cells. Lipid membranes also affect the ability of the efflux pump Pgp to bind and efflux anticancer drugs from cells. On the other hand, anticancer drugs can alter the structure and properties of lipid membranes, which are expected to influence the functioning of embedded proteins. The relevance of lipid model membranes to assess interactions between anticancer drugs and biomembranes is evidenced.

Research paper thumbnail of Novel self assembling nanoparticles for the oral administration of fondaparinux: Synthesis, characterization and in vivo evaluation

Research paper thumbnail of Self-assembly of polyisoprenoyl gemcitabine conjugates: Influence of supramolecular organization on their biological activity

An amphiphilic prodrug of gemcitabine, a cytidine analogue used clinically against various tumors... more An amphiphilic prodrug of gemcitabine, a cytidine analogue used clinically against various tumors, had been previously synthesized by covalent coupling to squalene, a natural isoprenoid chain. The resulting bioconjugate self-assembled spontaneously in water as nanoparticles, displaying an impressive activity both in vitro and in vivo. The aim of the present study was to determine the influence of the length of the isoprene moiety on the structure of the nanoparticles, in an attempt to establish a relationship between the chemical structure of the prodrug, its supramolecular organization, and its pharmacological activity. Remarkably, gemcitabine-squalene and gemcitabine-5-isoprenes, which differ only in the position of two methyl groups on the hydrophobic chain, displayed different supramolecular organizations and different anticancer activities on some cell lines. This difference in activity was related to the ability of nanoparticles to be internalized by cells.

Research paper thumbnail of Highly Swollen Liquid Crystals as New Reactors for the Synthesis of Nanomaterials

Chemistry of Materials, 2005

We present a new reacting medium called highly swollen liquid crystals (SLC) that exhibits hexago... more We present a new reacting medium called highly swollen liquid crystals (SLC) that exhibits hexagonal, cubic, or lamellar symmetry. These SLCs allowed us to synthesize nanostructured materials such as metal nanorods, oxide needles, or polymer micro-and ...

Research paper thumbnail of Improving the Antitumor Activity of Squalenoyl-Paclitaxel Conjugate Nanoassemblies by Manipulating the Linker between Paclitaxel and Squalene

Advanced Healthcare Materials, 2012

Research paper thumbnail of A new nanomedicine based on didanosine glycerolipidic prodrug enhances the long term accumulation of drug in a HIV sanctuary

International Journal of Pharmaceutics, 2011

Research paper thumbnail of Water Confined in Lamellar Structures of AOT Surfactants: An Infrared Investigation

The Journal of Physical Chemistry B, 2002

Research paper thumbnail of Structural and Thermal Characterization of Mono- and Diacyl Polyoxyethylene Glycol by Infrared Spectroscopy and X-ray Diffraction Coupled to Differential Calorimetry

The Journal of Physical Chemistry B, 2004

Research paper thumbnail of Solid-State Phase Transition of a Hydrated β-Cyclodextrin Dimeric Complex

The Journal of Physical Chemistry B, 2002

Research paper thumbnail of Protein Driven Patterning of Self-Assembled Cubosomic Nanostructures:  Long Oriented Nanoridges

The Journal of Physical Chemistry B, 2005

Research paper thumbnail of Self-Assembly of Squalene-Based Nucleolipids: Relating the Chemical Structure of the Bioconjugates to the Architecture of the Nanoparticles

Research paper thumbnail of EJOC Cover

Research paper thumbnail of Influence of the nanoprecipitation conditions on the supramolecular structure of squalenoyled nanoparticles

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Jan 22, 2015

Hydrophobic organic compounds dissolved in a polar solvent can self-assemble into nanoparticles (... more Hydrophobic organic compounds dissolved in a polar solvent can self-assemble into nanoparticles (NPs) upon nanoprecipitation into water. In the present study, we have investigated the structure of squalenacetyl-adenosine (SQAc-Ad) nanoparticles which were previously found to exhibit impressive neuroprotective activity. When obtained by nanoprecipitation of a SQAc-Ad ethanolic solution into water, two different supramolecular organizations of SQAc-Ad NPs were evidenced, depending on the water-to-ethanol volume ratio. It has been shown that a fraction of the solvent remained associated with the NPs, despite prolonged evaporation under reduced pressure after nanoprecipitation, and that this residual solvent dramatically affected their structure. This study points to the importance of being in the "Ouzo" region to minimize the amount and effect of residual solvent and to control the structure of NPs.

Research paper thumbnail of Novel self assembling nanoparticles for the oral administration of fondaparinux: Synthesis, characterization and in vivo evaluation

Journal of Controlled Release

Fondaparinux (Fpx) is the anticoagulant of choice in the treatment of short- and medium-term thro... more Fondaparinux (Fpx) is the anticoagulant of choice in the treatment of short- and medium-term thromboembolic disease. To overcome the low oral bioavailability of Fpx, a new nanoparticulate carrier has been developed. The nanoparticles (NPs) contain squalenyl derivatives, known for their excellent oral bioavailability. They spontaneously self-assemble upon both electrostatic and hydrophobic interactions between the polyanionic Fpx and cationic squalenyl (CSq) derivatives. The preparation conditions were optimized to obtain monodisperse, stable NPs with a mean diameter in the range of 150-200nm. The encapsulation efficiencies were around 80%. Fpx loadings reached 39wt.%. According to structural and morphological analysis, Fpx and CSq organized in spherical multilamellar ("onion-type") nanoparticles. Furthermore, in vivo studies in rats suggested that Fpx was well absorbed from the orally administered NPs, which totally dissociated when reaching the blood stream, leading to th...

Research paper thumbnail of Nanostructures and polymorphisms in protein stabilised lipid nanoparticles, as food bioactive carriers: contribution of particle size and adsorbed materials

Procedia Food Science, 2011

Research paper thumbnail of Surface modified Mg-doped ZnO QDs for biological imaging

European Journal of Nanomedicine, 2015

Research paper thumbnail of Structural and thermal characterization of glyceryl behenate by X-ray diffraction coupled to differential calorimetry and infrared spectroscopy

International journal of pharmaceutics, Jan 24, 2007

Physical and thermal properties of glyceryl behenate (Compritol 888 ATO) used as sustained-releas... more Physical and thermal properties of glyceryl behenate (Compritol 888 ATO) used as sustained-release matrix in pharmaceutical applications are studied by coupled time-resolved synchrotron X-ray diffraction and Differential Scanning Calorimetry combined with Infrared Spectroscopy. With these techniques, all polymorphs formed in glyceryl behenate, analyzed as received and after various thermal treatments from quenching to slow crystallization, are characterized. By using different well-controlled mixtures of mono-, di- and tribehenate, we identify each lamellar phase observed in the glyceryl behenate. Finally the influence of the crystallization rate on the formation of preferential conformations was also analyzed in order to bring insights into the polymorphism of glyceryl behenate. By changing the crystallization rate of the sample, it was shown that one can favor the formation of preferential polymorphs in the sample. In particular the crystallization at 10 degrees C/min seems to be ...

Research paper thumbnail of Unsaturated fatty acid enriched vs. control milk triacylglycerols: Solid and liquid TAG phases examined by synchrotron radiation X-ray diffraction coupled with DSC

Food Research International, 2015

ABSTRACT The fatty acid composition of milk triacylglycerols (TAGs) can be modified to improve th... more ABSTRACT The fatty acid composition of milk triacylglycerols (TAGs) can be modified to improve their nutritional properties and the long-term health of consumers. However, the consequences of an increase in unsaturated fatty acid (UFA) content on the physical properties of milk TAGs remain to be elucidated. This study aimed at comparing the crystallisation properties and melting behaviour of control vs. UFA-enriched milk TAGs using the coupling of time-resolved synchrotron X-ray diffraction and differential scanning calorimetry on cooling and then heating at 3 °C/min. On cooling from the melt, high crystallisation temperature (HCT) TAGs solidify from 15.8 °C in α 2L (45–49 Å) structures, then low crystallisation temperature (LCT) TAGs form α 3L structures with a higher thickness (75.5 Å vs. 71.5 Å) and a delay (8.5 °C vs. 12.1 °C) for UFA-enriched TAG. On heating, melting of TAGs crystals and formation of 3L2 (64.7–80.1 Å) and β′ 2Lf (40–44 Å) crystals associated with polymorphic reorganisations have been characterised. The organisation of TAG molecules in their liquid state revealed a higher thickness for UFA-enriched TAGs as compared to control TAGs. Such results improve the knowledge about the mechanisms of TAG crystallisation as a function of their FA composition and are important for the technological utilisation of UFA-enriched TAGs in food products.

Research paper thumbnail of Lipidic spherulites as magnetic resonance imaging contrast agents

New J. Chem., 2014

ABSTRACT Magnetic resonance imaging is an excellent technique to achieve anatomical details and h... more ABSTRACT Magnetic resonance imaging is an excellent technique to achieve anatomical details and highly resolved images. The search for efficient contrast agents to increase the signal to background ratio led us to evaluate paramagnetic spherulites as potential Magnetic Resonance Imaging (MRI) contrast agents. Spherulites are supramolecular assemblies, made of lipidic concentric multilayers, able to encapsulate with high efficiency soluble macromolecules. Despite their highly interesting structure, spherulites have never been proposed as imaging agents. We proposed here three approaches to render spherulites paramagnetic: encapsulating a soluble contrastophore, inserting a lipidic contrastophore derivative or grafting a soluble contrastophore at the surface of the spherulites. Following similar strategies, liposomes were prepared for comparison. The conservation of the spherulite structure, throughout these three strategies, was shown by cryoelectron microscopy and small angle light scattering. The effect of the paramagnetic spherulites was studied by magnetic resonance imaging at different magnetic fields. The results showed that insertion of a contrastophore lipidic derivative into spherulite bilayers and grafting a contrastophore at the surface of the spherulites were the two strategies which led to the highest MRI contrast improvement.

Research paper thumbnail of Liposomal formulation of a glycerolipidic prodrug for lymphatic delivery of didanosine via oral route

Didanosine is a polar drug with poor membrane absorption and high hepatic first pass metabolism. ... more Didanosine is a polar drug with poor membrane absorption and high hepatic first pass metabolism. This study aimed at developing a lipidic formulation of a glycerolipidic prodrug of didanosine in order to improve its bioavailability. In the course of a preformulation study, the glycerolipidic prodrug of didanosine was characterized by microscopy, DSC and XRDT. In anhydrous conditions, the prodrug displayed a polymorphic behaviour similar to that of triglycerides. Then, we evaluated three types of lipidic formulations (emulsions, mixed micelles and liposomes) in order to encapsulate the prodrug. Solubilities in water - even in the presence of taurocholate micelles - but also in some oils were very low (max 244 microg/mL) as the prodrug was found to be amphiphilic (log P=2). On the contrary, the prodrug was found to be perfectly incorporated in dipalmitoylphosphatidylcholine (DPPC) multilamellar liposomes up to a ratio of 1:5 (mol:mol) prodrug:DPPC as suggested by HPLC-UV and DSC experiments. Moreover, these liposomes could be freeze-dried whereas the chemical integrity of the prodrug was preserved. Then, the freeze-dried liposomal preparation could be formulated as gastro-resistant capsules to prevent didanosine from acidic degradation. Further experiments are on the way to evaluate in vitro the absorption of prodrug incorporated in liposomes by enterocytes.

Research paper thumbnail of Interactions of anticancer drugs with biomembranes: What can we learn from model membranes?

The interactions of anticancer drugs with cell membranes are of primary importance for drug trans... more The interactions of anticancer drugs with cell membranes are of primary importance for drug transport, accumulation and activity. However, these interactions are very difficult to investigate because of the complexity of biological membranes. Lipid model membranes have therefore been built to gain insight into the collective role of lipids in drug-membrane interactions. Membranes can act as a barrier for drug molecules, sequester them or conversely may allow them to freely diffuse, thereby modulating the accumulation of drugs into cells. Lipid membranes also affect the ability of the efflux pump Pgp to bind and efflux anticancer drugs from cells. On the other hand, anticancer drugs can alter the structure and properties of lipid membranes, which are expected to influence the functioning of embedded proteins. The relevance of lipid model membranes to assess interactions between anticancer drugs and biomembranes is evidenced.

Research paper thumbnail of Novel self assembling nanoparticles for the oral administration of fondaparinux: Synthesis, characterization and in vivo evaluation

Research paper thumbnail of Self-assembly of polyisoprenoyl gemcitabine conjugates: Influence of supramolecular organization on their biological activity

An amphiphilic prodrug of gemcitabine, a cytidine analogue used clinically against various tumors... more An amphiphilic prodrug of gemcitabine, a cytidine analogue used clinically against various tumors, had been previously synthesized by covalent coupling to squalene, a natural isoprenoid chain. The resulting bioconjugate self-assembled spontaneously in water as nanoparticles, displaying an impressive activity both in vitro and in vivo. The aim of the present study was to determine the influence of the length of the isoprene moiety on the structure of the nanoparticles, in an attempt to establish a relationship between the chemical structure of the prodrug, its supramolecular organization, and its pharmacological activity. Remarkably, gemcitabine-squalene and gemcitabine-5-isoprenes, which differ only in the position of two methyl groups on the hydrophobic chain, displayed different supramolecular organizations and different anticancer activities on some cell lines. This difference in activity was related to the ability of nanoparticles to be internalized by cells.

Research paper thumbnail of Highly Swollen Liquid Crystals as New Reactors for the Synthesis of Nanomaterials

Chemistry of Materials, 2005

We present a new reacting medium called highly swollen liquid crystals (SLC) that exhibits hexago... more We present a new reacting medium called highly swollen liquid crystals (SLC) that exhibits hexagonal, cubic, or lamellar symmetry. These SLCs allowed us to synthesize nanostructured materials such as metal nanorods, oxide needles, or polymer micro-and ...

Research paper thumbnail of Improving the Antitumor Activity of Squalenoyl-Paclitaxel Conjugate Nanoassemblies by Manipulating the Linker between Paclitaxel and Squalene

Advanced Healthcare Materials, 2012

Research paper thumbnail of A new nanomedicine based on didanosine glycerolipidic prodrug enhances the long term accumulation of drug in a HIV sanctuary

International Journal of Pharmaceutics, 2011

Research paper thumbnail of Water Confined in Lamellar Structures of AOT Surfactants: An Infrared Investigation

The Journal of Physical Chemistry B, 2002

Research paper thumbnail of Structural and Thermal Characterization of Mono- and Diacyl Polyoxyethylene Glycol by Infrared Spectroscopy and X-ray Diffraction Coupled to Differential Calorimetry

The Journal of Physical Chemistry B, 2004

Research paper thumbnail of Solid-State Phase Transition of a Hydrated β-Cyclodextrin Dimeric Complex

The Journal of Physical Chemistry B, 2002

Research paper thumbnail of Protein Driven Patterning of Self-Assembled Cubosomic Nanostructures:  Long Oriented Nanoridges

The Journal of Physical Chemistry B, 2005