Papers by Isabelle Texier
Journal of Colloid and Interface Science, Aug 1, 2011
Lipid nanoparticles (LNP) have been designed based on low cost and human-use approved excipients,... more Lipid nanoparticles (LNP) have been designed based on low cost and human-use approved excipients, and manufactured by an easy, robust, and up-scalable process. Fluid colloidal dispersions or gel viscous formulations of highly stable nanoparticles (more than 12 month stability is achieved for some formulations) can be obtained. Their physicochemical properties are studied by Dynamic Light Scattering, Differential Scanning Calorimetry, and NMR. The results picture nanoparticles with a non-crystalline core, which viscosity can be finely tuned by the lipid composition and the temperature. A design of experiments has been used to investigate the limits of the system colloidal stability. The impact of core and surfactant weight fractions have been explored both experimentally and using the design of experiments. The versatility of this physicochemical system could open the way to a wide range of future pharmaceutical applications.
Drug Delivery and Translational Research
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.
Microscopy and Microanalysis, 2018
Nanomedicine: Nanotechnology, Biology and Medicine, 2020
Autoradiography of 64 Cu-labelled nanostructured lipid carriers (NLC) and Oil Red O histology (ne... more Autoradiography of 64 Cu-labelled nanostructured lipid carriers (NLC) and Oil Red O histology (neutral lipids staining) of aortas showed significant particle uptake in atherosclerotic lesions 24 h after injection in ApoE −/− mice atherosclerotic models. Produced by well-controlled and up-scalable high pressure homogenization, NLC could present similar features than lipoproteins, and be used as synthetic mimetics to convey drugs and contrast agents to atherosclerotic lesions.
Nanotoxicology, 2018
The objective of our work was to investigate the effects of different types of nanoparticles on e... more The objective of our work was to investigate the effects of different types of nanoparticles on endothelial (HUVEC) and monocytic cell functions. We prepared and tested 14 different nanosystems comprising liposomes, lipid nanoparticles, polymer and iron oxide nanoparticles. Some of the tested nanosystems contained targeting, therapeutic, or contrast agent(s). The effect of particles (0-400 µg/mL) on endothelial-monocytic cell interactions in response to TNF-α was investigated using an arterial bifurcation model and dynamic monocyte adhesion assay. Spontaneous HUVEC migration (0-100 µg/mL nanoparticles) and chemotaxis of monocytic cells towards MCP-1 in presence of particles (0-400 µg/mL) were determined using a barrier assay and a modified Boyden chamber assay, respectively. Lipid nanoparticles dose-dependently reduced monocytic cell chemotaxis and adhesion to activated HUVECs. Liposomal nanoparticles had little effect on cell migration, but one formulation induced monocytic cell recruitment by HUVECs under non-uniform shear stress by about 50%. Fucoidan-coated polymer nanoparticles (25-50 µg/mL) inhibited HUVEC migration and monocytic cell chemotaxis, and had a suppressive effect on monocytic cell recruitment under non-uniform shear stress. No significant effects of iron oxide nanoparticles on monocytic cell recruitment were observed except lauric acid and human albumin-coated particles which increased endothelial-monocytic interactions by 60-70%. Some of the iron oxide nanoparticles inhibited HUVEC migration and monocytic cell chemotaxis. These nanoparticle-induced effects are of importance for vascular cell biology and function and must be considered before the potential clinical use of some of the analyzed nanosystems in cardiovascular applications.
Molecular Pharmaceutics, 2019
Particle size distribution and stability are key attributes for the evaluation of the safety and ... more Particle size distribution and stability are key attributes for the evaluation of the safety and efficacy profile of medical nanoparticles (Med-NPs). Measuring particle average size and particle size distribution is a challenging task which requires the combination of orthogonal high-resolution sizing techniques, especially in complex biological media. Unfortunately, despite its limitations, due to its accessibility, low cost, and easy handling, batch mode dynamic light scattering (DLS) is still very often used as the only approach to measure particle size distribution in the nanomedicine field. In this work the use of asymmetric flow field flow fractionation coupled to multiangle light scattering and dynamic light scattering detectors (AF4-MALS-DLS) was evaluated as an alternative to batch mode DLS to measure the physical properties of lipid-based nanoparticles. A robust standard operating procedure (SOPs) developed by the Nanomedicine Characterization Laboratory (EUNCL) was presented and tested to assess size stability, batch to batch consistency, and the behavior of the lipid-based nanoparticles in plasma. Orthogonal sizing techniques, such as transmission electron microscopy (TEM) and particle tracking analysis (PTA) measurements, were performed to support the results. While batch mode DLS could be applied as a fast and simple method to provide a preliminary insight into the integrity and polydispersity of samples, it was unsuitable to resolve small modifications of the particle size distribution. The introduction of nanoparticle sorting by fieldflow fractionation coupled to online DLS and MALS allowed assessment of batch to batch variability and changes in the size of the lipid nanoparticles induced by the interaction with serum proteins, which are critical for quality control and regulatory aspects. In conclusion, if a robust SOP is followed, AF4-MALS-DLS is a powerful method for the preclinical characterization of lipid-based nanoparticles.
Carbohydrate Polymers, 2017
Highlights A novel class of chitosan sponges consisting of a semi-interpenetrating network of c... more Highlights A novel class of chitosan sponges consisting of a semi-interpenetrating network of chitosan (CS) and poly(ethylene glycol) (PEG) was developed The semi-interpenetrating chitosan CS/PEG sponges were designed by crosslinking PEG in the CS matrix via a thiol-yne coupling reaction performed in physiological conditions The formation of the crosslinked PEG network imparted exceptional characteristics to the CS sponges, including a structure with large interconnected pores, improved mechanical properties and stability at physiological pH
Journal of Colloid and Interface Science, 2018
To benefit from the biocompatibility of lipid nanoparticles associated with the transfection abil... more To benefit from the biocompatibility of lipid nanoparticles associated with the transfection ability of chitosan, small chitosan lipid nanoparticles (CS-LNPs) dedicated to SiRNA delivery were formulated by an easy-to-implement one-step process. Formulations of CS-LNPs (lipid core stabilized by a shell comprising phospholipids/cationic lipids and hydrophobically modified chitosan) were optimized for their physico-chemical properties (size, zeta potential, colloidal stability) according to their shell composition. In particular, amphiphilic chitosan with various molecular weight and C12 degrees of substitution, and different phospholipids and cationic lipids (lecithin, DOTAP, DOPE) were included at the particle surface at different ratios. The ability of the particles for SiRNA complexation, NIH3T3 cell transfection, and ERK1 downregulation, were studied. Lipid nanoparticles formulated with 15,000 g/mol 2% C12 substituted chitosan, DOTAP and DOPE, mediated 40% ERK1 downregulation efficiency, comparable to lipofectamine™ RNAimax, while displaying no cytotoxicity up to 500 µg/mL.
Macromolecular bioscience, Jan 3, 2017
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.
Polymer International, 2017
Chitosan (CS) has received much attention as a functional biopolymer for designing various hydrog... more Chitosan (CS) has received much attention as a functional biopolymer for designing various hydrogels for biomedical applications. This review provides an overview of the different types of CS‐based hydrogels, the approaches that can be used to fabricate hydrogel matrices with specific features and their applications in controlled drug delivery and tissue engineering. Emphasis is laid on the recent design concepts of hybrid hydrogels based on mixtures of CS and natural or synthetic polymers, interpenetrating polymer networks as well as composite hydrogels prepared by embedding nanoparticles into CS matrices. © 2017 Society of Chemical Industry
Biofutur, 2010
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.
Http Www Theses Fr, 1999
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.
Translational Research, 2016
The objective was to prospectively evaluate the application of intraoperative fluorescence imagin... more The objective was to prospectively evaluate the application of intraoperative fluorescence imaging (IOFI) in the surgical excision of malignant masses in dogs, using a novel lipid nanoparticle contrast agent. Dogs presenting with spontaneous softtissue sarcoma or subcutaneous tumors were prospectively enrolled. Clinical staging and whole-body computed tomography (CT) were performed. All the dogs received an intravenous injection of dye-loaded lipid nanoparticles, LipImage 815. Wide or radical resection was realized after CT examination. Real-time IOFI was performed before skin incision and after tumor excision. In cases of radical resection, the lymph nodes (LNs) were imaged. The margin/healthy tissues fluorescence ratio or LN/ healthy tissues fluorescence ratio was measured and compared with the histologic margins or LN status. Nine dogs were included. Limb amputation was performed in 3 dogs, and wide resection in 6. No adverse effect was noted. Fluorescence was observed in all 9 of the tumors. The margins were clean in 5 of 6 dogs after wide surgical resection, and the margin/healthy tissues fluorescence ratio was close to 1.0 in all these dogs. Infiltrated margins were observed in 1 case, with a margin/healthy tissues fluorescence ratio of 3.2. Metastasis was confirmed in 2 of 3 LNs, associated with LN/healthy tissues fluorescence ratios of 2.1 and 4.2, whereas nonmetastatic LN was associated with a ratio of 1.0. LipImage 815 used as a contrast agent during IOFI seemed to allow for good discrimination between tumoral and healthy tissues. Future studies are scheduled to evaluate the sensitivity and specificity of IOFI using LipImage 815 as a tracer.
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.
Radiation Physics and Chemistry, 1997
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
This paper describes the SWAN-iCare system and its potential impact in the area of wound manageme... more This paper describes the SWAN-iCare system and its potential impact in the area of wound management. The SWAN-iCare project aims at developing an integrated autonomous device for the monitoring and the personalized management of chronic wounds, mainly diabetic foot ulcers and venous leg ulcers. Most foot and leg ulcers are caused by diabetes and vascular problems respectively but a remarkable number of them are also due to the co-morbidity influence of many other diseases (e.g. kidney disease, congestive heart failure, high blood pressure, inflammatory bowel disease). More than 10 million people in Europe suffer from chronic wounds, a number which is expected to grow due to the aging of the population. The core of the project is the fabrication of a conceptually new wearable negative pressure device equipped with Information and Communication Technologies. Such device will allow users to: (a) accurately monitor many wound parameters via non-invasive integrated micro-sensors, (b) early identify infections and (c) remotely provide an innovative personalized two-line therapy via non-invasive micro-actuators to supplement the negative pressure wound therapy.
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Papers by Isabelle Texier