Research experience
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Jan 2002–
Dec 2012Research: Université d'Angers
Université d'Angers · MINT (Micro et nanomédecines en thérapeutique)France · Angers
Publications (32) View all
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Article: In vitro and in vivo evaluation of superparamagnetic iron oxide nanoparticles coated by bisphosphonates: the effects of electrical charge and molecule length.
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ABSTRACT: Physicochemical coating properties are often considered to be determining factors for in vivo characteristics of superparamagnetic iron oxide nanoparticles, used as contrast agent in Magnetic Resonance Imaging (MRI). To investigate the electrical charge (modified by zero, one or two ammonium groups) and the molecule length (3, 5 or 7 methylene chains) effects of bisphosphonate-type coatings, we assessed the complement activation, in vivo plasma and tissue relaxation time alterations of intravenously injected small iron oxide nanoparticles (< 25 nm) on male healthy Wistar rats. The presence of ammonium groups induces a weak activation of the complement whatever the size and the concentration of particles, whereas hydroxyethylenebisphosphonate (HEBP)-coated particles are poor complement activators only at the lowest concentration. In vivo, HEBP-coated nanoparticles have the greatest prolonged relaxation time effects, despite their higher negative electrical charge, contrary to two ammonium bearing coatings. No significant differences were observed between mono-ammonium molecular coatings.European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 02/2013; · 2.61 Impact Factor -
Article: Lysozyme Encapsulation Within PLGA and CaCO3 Microparticles Using Supercritical CO2 Medium
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ABSTRACT: This study is part of a global project which aims at conceiving and characterizing implantable synthetic extracellular matrices seeded with multifunctional particles for bone and cartilage tissue engineering. To date, protein encapsulation remains a challenge in the field of microencapsulation. The aim of this work is to use supercritical CO2 to generate polymeric and inorganic particles for protein encapsulation. Poly(lactic-co-glycolic) (PLGA) and calcium carbonate (CaCO3) microparticles were chosen to be investigated. In both cases, spherical particles were successfully obtained based on the formation of an emulsion in CO2 media. Most importantly, only non-toxic solvents or aqueous solution were used for the formulation of microparticles. Encapsulation experiments were carried out to provide a proof of concept. Lysozyme was chosen as a model protein and experimental designs were made in order to better understandthe system and to better predict the encapsulation yield. The encapsulation yield can reach about 60% in both cases. The mechanism of particle formation and lysozyme encapsulation will also be discussed in detail.Journal of Supercritical Fluids The 01/2013; · 2.86 Impact Factor -
Article: New starch-based radiotracer for lung perfusion scintigraphy
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ABSTRACT: PurposeIn order to avoid the microbiological risks linked to human serum albumin macroaggregates (MAA) used for lung perfusion scintigraphy, we developed a new starch-based Tc-99m potential radiopharmaceutical. MethodsMicroparticles were prepared from oxidised starch coupled to natural polyamine for Tc-99m complexation. Suspensions were formulated as ready-to-use kits for easy one-step labelling procedures. ResultsParticle-size analysis, electron microscopy, and confocal microscopy were performed for microparticle characterisation, and gave a typical size distribution ranging from 7 to 63µm, with a homogenous population of spherical or oval-shaped microparticles. Radiochemical purity exceeded 95%, and was stable for at least 8 h. When challenged with histidine and human plasma, labelling was also stable. Dynamic scintigraphic acquisitions and biodistribution studies conducted on healthy Wistar rats showed a tracer accumulation with more than 80% of the ID in the lungs after 15 min. ConclusionsWith clinically significant characteristics such as a lung half-life of 3 h, a lung-to-vascular ratio of 900, and a lung-to-liver ratio of 90, starch-based microparticles exhibit all the qualities for an effective new lung perfusion agent.European journal of nuclear medicine and molecular imaging 04/2012; 37(1):146-155. · 4.99 Impact Factor -
Article: Effect of chain length and electrical charge on properties of ammonium-bearing bisphosphonate-coated superparamagnetic iron oxide nanoparticles: formulation and physicochemical studies
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ABSTRACT: Bisphosphonates BP molecules have shown to be efficient for coating superparamagnetic iron oxide particles. In order to clarify the respective roles of electrical charge and the length of the molecules, bisphosphonates with one or two ammonium moieties with an intermediate aliphatic group of 3, 5 or 7 carbons were synthesized and iron oxide nanoparticles coated. The evaluation on their iron core properties was made by transmission electron microscopy (TEM), nuclear magnetic relaxation dispersion (NMRD) profiles and Mössbauer spectra. The core size is close to 5nm, with a global superparamagnetic behaviour modified by a paramagnetic Fe-based layer, probably due to surface crystal alteration. The hydrodynamic sizes increase slightly with aliphatic chain length (from 9.8 to 18.6nm). The presence of one or two ammonium group(s) lowers the negative electrophoretic mobility up to bear zero values but reduces their colloidal stability. These BP-coated iron oxide nanoparticles are promising Magnetic Resonance Imaging (MRI) contrast agents. KeywordsIron oxides-Contrast agents-Superparamagnetic behaviour-Bisphosphonates-NMRD profiles-Mössbauer spectrometry-Colloids-Magnetic Resonance ImagingJournal of Nanoparticle Research 04/2012; 12(4):1239-1248. · 3.29 Impact Factor -
Article: A starch-based microparticulate system dedicated to diagnostic and therapeutic nuclear medicine applications.
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ABSTRACT: The aim of this work was to develop a new microparticulate system able to form a complex with radionuclides with a high yield of purity for diagnostic or therapeutic applications. Owing to its properties potato starch was chosen as starting material and modified by oxidization and coupling of a ligand (polyamine) enabling modified starch to chelate radionuclides. The choice of suitable experiments was based on a combination of a Rechtschaffner experimental design and a surface response design to determine the influence of experimental parameters and to optimize the final product. Starch-based microparticle formulations from the experimental plans were compared and characterized through particle size analysis, scanning electron microscopy, elemental analysis and, for the most promising formulations, by in vitro labeling stability studies and determination of free polyamine content or in vivo imaging studies. The mechanism of starch-based microparticle degradation was identified by means of size measurements. The results of the Rechtschaffner design showed the positive qualitative effect of the temperature and the duration of coupling reaction whereas surface response analysis clearly showed that, by increasing the oxidization level and starch concentration, the nitrogen content in the final product is increased. In vitro and in vivo characterization led to identification of the best formulation. With a size around 30 μm, high radiochemical purity (over 95%) and a high signal-to-noise ratio (over 600), the new starch-based microparticulate system could be prepared as ready-to-use kits and sterilized without modification of its characteristics, and thus meet the requirement for in vivo diagnostic and therapeutic applications.Biomaterials 11/2011; 32(31):7999-8009. · 7.40 Impact Factor
