Biodistribution of nanoencapsulated bioactive compounds is primarily determined by the size, shap... more Biodistribution of nanoencapsulated bioactive compounds is primarily determined by the size, shape, chemical composition and surface properties of the encapsulating nanoparticle, and, thus, less dependent on the physicochemical properties of the active pharmaceutical ingredient encapsulated. In the current work, we aimed to investigate the impact of formulation type on biodistribution profile for two clinically relevant nanoformulations. We performed a comparative study of biodistribution in healthy rats at several dose levels and durations up to 14-day post-injection. The studied nanoformulations were nanostructured lipid carriers incorporating the fluorescent dye IR780-oleyl, and polymeric nanoparticles containing the anticancer agent cabazitaxel. The biodistribution was approximated by quantification of the cargo in blood and relevant organs. Several clear and systematic differences in biodistribution were observed, with the most pronounced being a much higher (more than 50-fold)...
A new technology for the encapsulation of lipophilic molecules -both drugs and contrast agentshas... more A new technology for the encapsulation of lipophilic molecules -both drugs and contrast agentshas been developed, based on oil-in-water nanoemulsions. Physicochemical characterizations of the nanoparticles evidence highly stable lipid nanoemulsions with amorphous core of temperatureand compositiontunable viscosity. Particles display low in vitro cytotoxicity (IC50 > 300 μg/mL of lipids), and high tolerance in vivo. They can be efficiently loaded with hydrophobic to amphiphilic molecules, such as fluorescent dyes for tumor labeling, photosensitizers for phototherapy, or chemotoxic drugs. The presence of PEGylated surfactants in the particle coating ensures a good in vivo stealthiness, as assessed by their biodistribution recorded using fluorescence imaging and radioactivity counting (C and H particle labeling). The lipid nanoparticles can moreover be functionalized by tumortargeting ligands, such as the cRGD peptide, to improve specific tumor cell accumulation.
A hybrid hydrogel composed of solid lipid nanoparticles (LNPs) entrapped within chemically cross-... more A hybrid hydrogel composed of solid lipid nanoparticles (LNPs) entrapped within chemically cross-linked carboxymethylcellulose (CMC) is developed to achieve localized and sustained release of lipophilic drugs. The analysis of LNP stability as well as the hydrogel swelling and mechanical properties confirm the successful incorporation of particles up to a concentration of 50% w/wCMC . The initial LNP release rate can be prolonged by increasing the particle diameter from 50 to 120 nm, while the amount of long-term release can be adjusted by tailoring the particle surface charge or the cross-linking density of the polymer. After 30 d, 58% of 50 nm diameter negatively charged LNPs escape from the matrix while only 17% of positively charged nanoparticles are released from materials with intermediate cross-linking density. A mathematical diffusion model based on Fick's second law is efficient to predict the diffusion of the particles from the hydrogels.
La chirurgie en oncologie sera un des premiers champs d'application clinique des recents prog... more La chirurgie en oncologie sera un des premiers champs d'application clinique des recents progres en imagerie de fluorescence. Le developpement de nouveaux traceurs ciblant les tumeurs et de systemes de mesures dans le proche infrarouge permet d'envisager d'assister le geste chirurgical lors de l'exerese de tumeurs et de la recherche de ganglions drainant une tumeur.
La photophysique des etats excites du decatungstate de sodium na 4w 1 0o 3 2 a ete etudiee dans l... more La photophysique des etats excites du decatungstate de sodium na 4w 1 0o 3 2 a ete etudiee dans l'eau et l'acetonitrile, a des echelles temporelles allant de la sub-picoseconde a quelques centaines de nanosecondes. L'absorption d'un photon dans la bande a transfert de charge de w 1 0o 4 3 2 induit la creation d'un etat excite primaire dans lequel les charges sont localisees. En moins de 50 ps, cet etat primaire donne naissance a un transitoire x dans lequel les charges seraient delocalisees sur plusieurs atomes de tungstene et/ou d'oxygene. Cette reaction ne peut etre decrite simplement par un schema precurseur-successeur. Il se produit vraisemblablement pendant cette etape des recombinaisons de charges non radiatives, et la reaction ne comporterait pas de barriere d'activation. Le transitoire x possede une duree de vie de 60 ns dans l'acetonitrile, 35 ns dans l'eau. Il reagit a l'echelle de la nanoseconde avec differents substrats, inorganiques ou organiques, par transfert d'electron ou arrachement d'atome h. Les constantes bimoleculaires de reaction et les rendements quantiques de formation des formes reduites w 1 0o 5 3 2/hw 1 0o 4 3 2 ont ete determinees pour de nombreuses familles de substrats. Une analogie entre la reactivite de ce transitoire x et celle des cetones a l'etat excite a ete proposee. L'activite photocatalytique de l'anion decatungstate pour la degradation solaire de pesticides dans l'eau a egalement ete demontree par photolyse continue, et comparee avec celle de tio 2. Les produits de photodegradation de l'atrazine ont ete determines. La photocatalyse par na 4w 1 0o 3 2 ne peut conduire seule a une mineralisation de cet herbicide, mais son couplage avec des methodes microbiologiques de degradation permet une mineralisation partielle du cycle aromatique de la molecule.
European Journal of Pharmaceutics and Biopharmaceutics, 2016
Near-infrared (NIR) fluorescence imaging using FDA-approved indocyanine green (ICG) has been the ... more Near-infrared (NIR) fluorescence imaging using FDA-approved indocyanine green (ICG) has been the subject of numerous studies during the past few years. It could constitute a potentially exciting new paradigm shift in veterinary oncology, especially to develop in vivo fluorescence imaging diagnostics and surgery guidance methods. The objective of this study was to evaluate the pharmacologic and toxicological characteristics in healthy beagle dogs of LipImage(TM) 815, a formulation made of NIR-dye-loaded lipid nanoparticles. The initial dosage for the evaluation of biodistribution was extrapolated from data in mice and then adapted to define the more adapted dose (MAD) according to the fluorescence results obtained in 5 dogs using a Fluobeam® 800 imaging device (phase 0 study). A single dose acute toxicity study was then performed (3 dogs, phase I study). Before the systemic administration of LipImage(TM) 815, the dogs presented a very mild residual fluorescence, particularly in the liver and kidneys. After injection, the plasma fluorescence continuously decreased, and the signal was relatively homogeneously distributed throughout the different organs, though more pronounced in the liver and to a lesser extent in the steroid-rich organs (adrenal, ovaries), intestines, lymph nodes and kidneys. A MAD of 2.0 μg/kg was found. No evidence of acute or delayed general, hepatic, renal or hematologic toxicity was observed at 1-fold, 5-fold or 10-fold MAD. The results of this phase-0/phase-I study showed that an optimal dosage of LipImage(TM) 815 of 2.0 μg/kg allowed the achievement of a fluorescence signal suitable for surgery guidance application without any acute side effects.
This paper summarizes the numerical contribution to a project for the detection of bioparticles p... more This paper summarizes the numerical contribution to a project for the detection of bioparticles present in a small volume of a liquid sample. Dielectrophoresis (DEP) is used to enhance their transport toward the surface of a detector. The mathematical model is composed of the complex electrokinetics equation for the DEP force field calculation and the advection-diffusion equation for the particle distribution inside the liquid sample. Three microdevices are studied: two coplanar electrode devices, the PIEM and the QM and a 3D configuration, the PM, which has been completely designed by numerical simulation performed with the Comsol Mutliphysics Finite Element code. To overcome problems of numerical instabilites diffusion when simulating the coplanar electrode devices, the DEP Collection Zone parameter is introduced. It appears as an effective computational tool to study these microsystems efficiency for collecting particles. Calculations have been confronted to experiments.
γ-irradiation and pulse radiolysis are used to check experimentally the ligand effect of the redo... more γ-irradiation and pulse radiolysis are used to check experimentally the ligand effect of the redox potential of the cyano-silver monomer couple Ag1(CN)2−/Ag0(CN)2- found to be lower than – 2.1 VNHE instead of equal to - 2.6 VNHE as in a previous theoretical evaluation (Remita et al., 1995, Journal of Physical Chemistry99, 13198). We present a mechanism explaining the reduction of Ag(CN)2− by the radical anion (CH3)2CO− indicating that the redox potential of the couple [2Ag1(CN)2−/Ag2+, xCN−] lies between - 2.1 and - 1.7 VNHE.
Proceedings of the 4th International Conference on Wireless Mobile Communication and Healthcare - "Transforming healthcare through innovations in mobile and wireless technologies", 2014
Biodistribution of nanoencapsulated bioactive compounds is primarily determined by the size, shap... more Biodistribution of nanoencapsulated bioactive compounds is primarily determined by the size, shape, chemical composition and surface properties of the encapsulating nanoparticle, and, thus, less dependent on the physicochemical properties of the active pharmaceutical ingredient encapsulated. In the current work, we aimed to investigate the impact of formulation type on biodistribution profile for two clinically relevant nanoformulations. We performed a comparative study of biodistribution in healthy rats at several dose levels and durations up to 14-day post-injection. The studied nanoformulations were nanostructured lipid carriers incorporating the fluorescent dye IR780-oleyl, and polymeric nanoparticles containing the anticancer agent cabazitaxel. The biodistribution was approximated by quantification of the cargo in blood and relevant organs. Several clear and systematic differences in biodistribution were observed, with the most pronounced being a much higher (more than 50-fold)...
A new technology for the encapsulation of lipophilic molecules -both drugs and contrast agentshas... more A new technology for the encapsulation of lipophilic molecules -both drugs and contrast agentshas been developed, based on oil-in-water nanoemulsions. Physicochemical characterizations of the nanoparticles evidence highly stable lipid nanoemulsions with amorphous core of temperatureand compositiontunable viscosity. Particles display low in vitro cytotoxicity (IC50 > 300 μg/mL of lipids), and high tolerance in vivo. They can be efficiently loaded with hydrophobic to amphiphilic molecules, such as fluorescent dyes for tumor labeling, photosensitizers for phototherapy, or chemotoxic drugs. The presence of PEGylated surfactants in the particle coating ensures a good in vivo stealthiness, as assessed by their biodistribution recorded using fluorescence imaging and radioactivity counting (C and H particle labeling). The lipid nanoparticles can moreover be functionalized by tumortargeting ligands, such as the cRGD peptide, to improve specific tumor cell accumulation.
A hybrid hydrogel composed of solid lipid nanoparticles (LNPs) entrapped within chemically cross-... more A hybrid hydrogel composed of solid lipid nanoparticles (LNPs) entrapped within chemically cross-linked carboxymethylcellulose (CMC) is developed to achieve localized and sustained release of lipophilic drugs. The analysis of LNP stability as well as the hydrogel swelling and mechanical properties confirm the successful incorporation of particles up to a concentration of 50% w/wCMC . The initial LNP release rate can be prolonged by increasing the particle diameter from 50 to 120 nm, while the amount of long-term release can be adjusted by tailoring the particle surface charge or the cross-linking density of the polymer. After 30 d, 58% of 50 nm diameter negatively charged LNPs escape from the matrix while only 17% of positively charged nanoparticles are released from materials with intermediate cross-linking density. A mathematical diffusion model based on Fick's second law is efficient to predict the diffusion of the particles from the hydrogels.
La chirurgie en oncologie sera un des premiers champs d'application clinique des recents prog... more La chirurgie en oncologie sera un des premiers champs d'application clinique des recents progres en imagerie de fluorescence. Le developpement de nouveaux traceurs ciblant les tumeurs et de systemes de mesures dans le proche infrarouge permet d'envisager d'assister le geste chirurgical lors de l'exerese de tumeurs et de la recherche de ganglions drainant une tumeur.
La photophysique des etats excites du decatungstate de sodium na 4w 1 0o 3 2 a ete etudiee dans l... more La photophysique des etats excites du decatungstate de sodium na 4w 1 0o 3 2 a ete etudiee dans l'eau et l'acetonitrile, a des echelles temporelles allant de la sub-picoseconde a quelques centaines de nanosecondes. L'absorption d'un photon dans la bande a transfert de charge de w 1 0o 4 3 2 induit la creation d'un etat excite primaire dans lequel les charges sont localisees. En moins de 50 ps, cet etat primaire donne naissance a un transitoire x dans lequel les charges seraient delocalisees sur plusieurs atomes de tungstene et/ou d'oxygene. Cette reaction ne peut etre decrite simplement par un schema precurseur-successeur. Il se produit vraisemblablement pendant cette etape des recombinaisons de charges non radiatives, et la reaction ne comporterait pas de barriere d'activation. Le transitoire x possede une duree de vie de 60 ns dans l'acetonitrile, 35 ns dans l'eau. Il reagit a l'echelle de la nanoseconde avec differents substrats, inorganiques ou organiques, par transfert d'electron ou arrachement d'atome h. Les constantes bimoleculaires de reaction et les rendements quantiques de formation des formes reduites w 1 0o 5 3 2/hw 1 0o 4 3 2 ont ete determinees pour de nombreuses familles de substrats. Une analogie entre la reactivite de ce transitoire x et celle des cetones a l'etat excite a ete proposee. L'activite photocatalytique de l'anion decatungstate pour la degradation solaire de pesticides dans l'eau a egalement ete demontree par photolyse continue, et comparee avec celle de tio 2. Les produits de photodegradation de l'atrazine ont ete determines. La photocatalyse par na 4w 1 0o 3 2 ne peut conduire seule a une mineralisation de cet herbicide, mais son couplage avec des methodes microbiologiques de degradation permet une mineralisation partielle du cycle aromatique de la molecule.
European Journal of Pharmaceutics and Biopharmaceutics, 2016
Near-infrared (NIR) fluorescence imaging using FDA-approved indocyanine green (ICG) has been the ... more Near-infrared (NIR) fluorescence imaging using FDA-approved indocyanine green (ICG) has been the subject of numerous studies during the past few years. It could constitute a potentially exciting new paradigm shift in veterinary oncology, especially to develop in vivo fluorescence imaging diagnostics and surgery guidance methods. The objective of this study was to evaluate the pharmacologic and toxicological characteristics in healthy beagle dogs of LipImage(TM) 815, a formulation made of NIR-dye-loaded lipid nanoparticles. The initial dosage for the evaluation of biodistribution was extrapolated from data in mice and then adapted to define the more adapted dose (MAD) according to the fluorescence results obtained in 5 dogs using a Fluobeam® 800 imaging device (phase 0 study). A single dose acute toxicity study was then performed (3 dogs, phase I study). Before the systemic administration of LipImage(TM) 815, the dogs presented a very mild residual fluorescence, particularly in the liver and kidneys. After injection, the plasma fluorescence continuously decreased, and the signal was relatively homogeneously distributed throughout the different organs, though more pronounced in the liver and to a lesser extent in the steroid-rich organs (adrenal, ovaries), intestines, lymph nodes and kidneys. A MAD of 2.0 μg/kg was found. No evidence of acute or delayed general, hepatic, renal or hematologic toxicity was observed at 1-fold, 5-fold or 10-fold MAD. The results of this phase-0/phase-I study showed that an optimal dosage of LipImage(TM) 815 of 2.0 μg/kg allowed the achievement of a fluorescence signal suitable for surgery guidance application without any acute side effects.
This paper summarizes the numerical contribution to a project for the detection of bioparticles p... more This paper summarizes the numerical contribution to a project for the detection of bioparticles present in a small volume of a liquid sample. Dielectrophoresis (DEP) is used to enhance their transport toward the surface of a detector. The mathematical model is composed of the complex electrokinetics equation for the DEP force field calculation and the advection-diffusion equation for the particle distribution inside the liquid sample. Three microdevices are studied: two coplanar electrode devices, the PIEM and the QM and a 3D configuration, the PM, which has been completely designed by numerical simulation performed with the Comsol Mutliphysics Finite Element code. To overcome problems of numerical instabilites diffusion when simulating the coplanar electrode devices, the DEP Collection Zone parameter is introduced. It appears as an effective computational tool to study these microsystems efficiency for collecting particles. Calculations have been confronted to experiments.
γ-irradiation and pulse radiolysis are used to check experimentally the ligand effect of the redo... more γ-irradiation and pulse radiolysis are used to check experimentally the ligand effect of the redox potential of the cyano-silver monomer couple Ag1(CN)2−/Ag0(CN)2- found to be lower than – 2.1 VNHE instead of equal to - 2.6 VNHE as in a previous theoretical evaluation (Remita et al., 1995, Journal of Physical Chemistry99, 13198). We present a mechanism explaining the reduction of Ag(CN)2− by the radical anion (CH3)2CO− indicating that the redox potential of the couple [2Ag1(CN)2−/Ag2+, xCN−] lies between - 2.1 and - 1.7 VNHE.
Proceedings of the 4th International Conference on Wireless Mobile Communication and Healthcare - "Transforming healthcare through innovations in mobile and wireless technologies", 2014
Uploads
Papers by Isabelle Texier