References of "Préat, Véronique"
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See detailDual anticancer drug/superparamagnetic iron oxide-loaded PLGA-based nanoparticles for cancer therapy and magnetic resonance imaging
Schleich, N.; Sibret, Pierre ULg; Danhier, P. et al

in International Journal of Pharmaceutics (2013), 447(1-2), 94-101

We developed dual paclitaxel (PTX)/superparamagnetic iron oxide (SPIO)-loaded PLGA-based nanoparticles for a theranostic purpose. Nanoparticles presented a spherical morphology and a size of 240 nm. The ... [more ▼]

We developed dual paclitaxel (PTX)/superparamagnetic iron oxide (SPIO)-loaded PLGA-based nanoparticles for a theranostic purpose. Nanoparticles presented a spherical morphology and a size of 240 nm. The PTX and iron loading were 1.84 ± 0.4 and 10.4 ± 1.93 mg/100 mg respectively. Relaxometry studies and phantom MRI demonstrated their efficacy as T2 contrast agent. Significant cellular uptake by CT26 cells of nanoparticles was shown by Prussian blue staining and fluorescent microscopy. While SPIO did not show any toxicity in CT-26 cells, PTX-loaded nanoparticles had a cytotoxic activity. PTX-loaded nanoparticle (5 mg/kg) with or without co-encapulated SPIO induced in vivo a regrowth delay of CT26 tumors. Together these multifunctional nanoparticles may be considered as future nanomedicine for simultaneous molecular imaging, drug delivery and real-time monitoring of therapeutic response. [less ▲]

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See detailDrug delivery to inflamed colon by nanoparticles: comparison of different strategies
Coco, Régis; Plapied, Laurence; Pourcelle, Vincent et al

in International Journal of Pharmaceutics (2013), 440(1), 3-12

For inflammatory bowel disease (IBD) treatment, local delivery of molecules loaded in nanoparticles to the inflamed colon could be a promising strategy. The aim of this study was to investigate how drug ... [more ▼]

For inflammatory bowel disease (IBD) treatment, local delivery of molecules loaded in nanoparticles to the inflamed colon could be a promising strategy. The aim of this study was to investigate how drug-loaded polymeric nanoparticles target the site of inflammation and to analyse the influence of different colon-specific delivery strategies. Three different polymeric nanoparticles were formulated using ovalbumin (OVA) as a model drug. pH-sensitive nanoparticles were made with Eudragit® S100. Mucoadhesive nanoparticles were created with trimethylchitosan (TMC). A mix of polymers, PLGA, PEG-PLGA and PEG-PCL, were used to obtain a sustained drug delivery. Furthermore, ligands targeting immune cells (i.e. mannose) or the inflamed colon (i.e. a specific peptide) were grafted on the PEG chain of PCL. Interaction of nanoparticles with the intestinal epithelium was explored using Caco-2 monolayers designed to mimic an inflamed epithelium and then visualized using confocal laser microscopy. TMC nanoparticles had the highest apparent permeability for OVA in the untreated model. However, in the inflamed model, there were no difference between TMC, PLGA-based and Eudragit® nanoparticles. The uptake of nanoparticles in the inflamed mouse colon was assessed in a horizontal diffusion chamber. Mannose-grafted PLGA nanoparticles showed the highest accumulation of OVA in inflamed colon. Based on these results, active targeting of macrophages and dendritic cells may be a promising approach for targeting the colon in IBD. [less ▲]

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See detailIn vitro investigations of smart drug delivery systems based on redox-sensitive cross-linked micelles
Cajot, Sébastien; Schol, D.; Dahnier, F. et al

in Macromolecular Symposia (2013), 13(12), 1661-1670

Redox-sensitive micelles are designed by using block copolymers of different architectures composed of a hydrophilic block of poly(ethylene oxide), and hydrophobic blocks of poly(ϵ-caprolactone) and poly ... [more ▼]

Redox-sensitive micelles are designed by using block copolymers of different architectures composed of a hydrophilic block of poly(ethylene oxide), and hydrophobic blocks of poly(ϵ-caprolactone) and poly(α-azide-ϵ-caprolactone). Stability of these micelles is insured in diluted media by cross-linking their core via the addition of a bifunctional cross-linker, while redox sensitivity is provided to these micelles by inserting a disulfide bridge in the cross-linker. The potential of these responsive micelles to be used as nanocarriers is studied in terms of cytotoxicity and cellular internalization. The release profiles are also investigated by varying the environment reductive strength. [less ▲]

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See detailTocol modified glycol chitosan for the oral delivery of poorly soluble drugs
Duhem, Nicolas; Rolland, Julien; Riva, Raphaël ULg et al

in International Journal of Pharmaceutics (2012), 423(2), 452-460

The aim of this study was to develop tocol derivatives of chitosan able (i) to self-assemble in the gastrointestinal tract and (ii) to enhance the solubility of poorly soluble drugs. Among the derivatives ... [more ▼]

The aim of this study was to develop tocol derivatives of chitosan able (i) to self-assemble in the gastrointestinal tract and (ii) to enhance the solubility of poorly soluble drugs. Among the derivatives synthesized, tocopherol succinate glycol chitosan (GC-TOS) conjugates spontaneously formed micelles in aqueous solution with a critical micelle concentration of 2 μg mL−1. AFM and TEM analysis showed that spherical micelles were formed. The GC-TOS increased water solubility of 2 model class II drugs. GC-TOS loading efficiency was 2.4% (w/w) for ketoconazole and 0.14% (w/w) for itraconazole, respectively. GC-TOS was non-cytotoxic at concentrations up to 10 mg mL−1. A 3.4-fold increase of the apparent permeation coefficient of ketoconazole across a Caco-2 cell monolayer was demonstrated. Tocol polymer conjugates may be promising vehicles for the oral delivery of poorly soluble drugs. [less ▲]

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See detailTargeting of tumor endothelium by RGD-grafted PLGA-nanoparticles
Danhier, Fabienne; Pourcelle, Vincent; Marchand-Brynaert, Jacqueline et al

in Düzgüneş, Nejat (Ed.) Methods in Enzymology: Nanomedicine — Cancer, Diabetes, and Cardiovascular, Central Nervous System, Pulmonary and Inflammatory Diseases (2012)

The destruction of the neovessels in solid tumors can cause the death of tumor cells resulting from the lack of oxygen and nutrients. Peculiarities of the tumor vasculature, however, also position ... [more ▼]

The destruction of the neovessels in solid tumors can cause the death of tumor cells resulting from the lack of oxygen and nutrients. Peculiarities of the tumor vasculature, however, also position angiogenic endothelial cells as obvious targets to address cytotoxic drugs into the tumor. In particular, the identification of a three-amino acids sequence, arginine-glycine-aspartate (RGD), as a fundamental recognition site for proliferating endothelial attachment to the extracellular matrix leads to the development of tumor-targeting ligands for nanoparticles. The RGD peptide can target the αvβ3 integrin overexpressed by the tumor endothelium, and thereby increases the accumulation of drug-loaded RGD-grafted nanoparticles. RGD-nanoparticles may thus extravasate more efficiently and enter the tumor via the enhanced permeability and retention (EPR) effect. This combination of active and passive processes leads to the penetration of nanoparticles into the tumor tissue, followed by cellular uptake and intracellular delivery of the cytotoxic payload. Since cancer cells may also express αvβ3 integrin, the entrapping of RGD-nanoparticles into the tumor interstitial fluid may yet be facilitated through direct binding to cancer cells. Here, we describe methods used for the preparation of RGD-nanoparticles and for the validation of their potential of tumor endothelium targeting both in vitro and in vivo. We also illustrate how RGD-nanoparticles may be more suited than nontargeted modalities for the tumor delivery of poorly soluble and/or highly cytotoxic drugs, using different mouse tumor xenograft models. [less ▲]

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See detailDesign of reversibly disulfide core cross-linked polymer micelles
Cajot, Sébastien ULg; Schol, Daureen ULg; Danhier, F. et al

Poster (2011, December 07)

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See detailDesign of reversibly disulfide core cross-linked polymer micelles
Cajot, Sébastien ULg; Schol, Daureen ULg; Danhier, F. et al

Poster (2011, November 21)

Over the last decade, polymer micelles attracted an increasing interest in drug pharmaceutical research because they could be used as efficient drug delivery systems. Micelles of amphiphilic block ... [more ▼]

Over the last decade, polymer micelles attracted an increasing interest in drug pharmaceutical research because they could be used as efficient drug delivery systems. Micelles of amphiphilic block copolymers are supramolecular core-shell type assemblies of tens of nanometers in diameter. An accumulation of polymer nanocarriers to solid tumours is possible due to the EPR effect. Even if micelles get a high stability in aqueous media, the dissociation of micelles is not always preserved when they are injected in the blood compartment. This work aims at reporting on the design of reversibly cross-linked micelles based on PEO-b-PCL copolymers by introducing disulfide bridges in the micelle core to provide higher stability. Different kinds of macromolecular architectures are employed to study their impact on the micelles and their biological behavior. These new functional copolymers were all successfully micellized, reversibly cross-linked and are stealthy, which show the efficiency of the developed cross-linking process and offer a set of nanocarriers to be tested further, as shown on the first biological tests. [less ▲]

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See detailDisulfide bridges, new prospect in drug delivery systems?
Cajot, Sébastien ULg; Danhier, F.; Schol, Daureen ULg et al

Poster (2011, September 03)

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See detailReversibly core-cross-linked micelles sensitive to reductive environment for the design of drug delivery systems
Cajot, Sébastien ULg; Danhier, F.; Collodoro, M. et al

Poster (2011, June 16)

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See detailNovel drug delivery sytem of siRNA based on chitosan, pegylated chitosan and polyethyleneimine
Ragelle, Héloïse; Vandermeulen, Gaëlle; Riva, Raphaël ULg et al

in Human Gene Therapy (2011, June 06), 22

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See detailSynthesis and characterization of reversibly core cross-linked micelles sensitive to reductive environment
Cajot, Sébastien ULg; Danhier, F.; Collodoro, M. et al

Poster (2011, May 12)

Detailed reference viewed: 38 (14 ULg)
See detailNovel amphiphilic copolymers and design of smart nanoparticles for drug delivery systems
Cajot, Sébastien ULg; Danhier, F.; Lautram, N. et al

Poster (2011, April 29)

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See detailFluorescent labeling of degradable poly(lactide-co-glycolide) for cellular nanoparticles tracking in living cells
Freichels, Hélène; Danhier, Fabienne; Préat, Véronique et al

in International Journal of Artificial Organs (2011), 34(2), 152-160

Fluorescent-labeled aliphatic polyesters are essential materials for in vitro and in vivo studies of the behavior of these biodegradable polymers in interaction with cells or in a body. In particular, the ... [more ▼]

Fluorescent-labeled aliphatic polyesters are essential materials for in vitro and in vivo studies of the behavior of these biodegradable polymers in interaction with cells or in a body. In particular, the direct cellular localization of drug delivery systems based on these materials allows better understanding of the internalization mechanism and determination of the pharmacokinetics. Polylactide-co-glycolide (PLGA) is a rapidly degradable copolymer widely used in pharmaceutics and nanomedecine. It was prepared by ring-opening polymerization of lactide and glycolide in order to obtain a well-defined material to investigate conditions allowing the covalent linkage of a fluorescent dye (fluorescein) while preserving the macromolecular characteristics of the polymer. The success of the functionalization was ascertained by proton nuclear magnetic resonance (1H NMR), size-exclusion chromatography (SEC) and fluorescence spectroscopy. [less ▲]

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See detailChitosan and chitosan derivatives in drug delivery and tissue engineering
Riva, Raphaël ULg; Raguelle, Héloïse; des Rieux, Anne et al

in Jayakumar, Rangasamy; Prabaharan, M.; Muzzarelli, Ricardo A. A. (Eds.) Chitosan for Biomaterials II (2011)

Chitosan is a nontoxic, biodegradable, and biocompatible polysaccharide of β(1-4)-linked d-glucosamine and N-acetyl-d-glucosamine. This derivative of natural chitin presents remarkable properties that ... [more ▼]

Chitosan is a nontoxic, biodegradable, and biocompatible polysaccharide of β(1-4)-linked d-glucosamine and N-acetyl-d-glucosamine. This derivative of natural chitin presents remarkable properties that have paved the way for the introduction of chitosan in the biomedical and pharmaceutical fields. Nevertheless, the properties of chitosan, such as its poor solubility in water or in organic solvents, can limit its utilization for a specific application. An elegant way to improve or to impart new properties to chitosan is the chemical modification of the chain, generally by grafting of functional groups, without modification of the initial skeleton in order to conserve the original properties. The functionalization is carried out on the primary amine group, generally by quaternization, or on the hydroxyl group. This review aims to provide an overview of chitosan and chitosan derivatives used for drug delivery, with a special emphasis on chemical modifications of chitosan to achieve specific biomedical purpose. The synthesis of the main chitosan derivatives will be reviewed. The applications of chitosan and these chitosan derivatives will be illustrated. [less ▲]

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See detailSynthesis of core cross-linked micelles for the development of new drug delivery systems
Cajot, Sébastien ULg; Danhier, F.; Lautram, N. et al

Poster (2010, October 29)

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See detailIn vitro identification of targeting ligands of human M cells by phage display
Fievez, V.; Plapied, L.; Plaideau, C. et al

in International Journal of Pharmaceutics (2010), 394(1-2), 35-42

To improve transport of vaccine-loaded nanoparticles, the phage display technology was used to identify novel lead peptides targeting human M cells. Using an in vitro model of the human follicle ... [more ▼]

To improve transport of vaccine-loaded nanoparticles, the phage display technology was used to identify novel lead peptides targeting human M cells. Using an in vitro model of the human follicle-associated epithelium (FAE) which contains both Caco-2 and M cells, a T7 phage display library was screened for its ability either to bind the apical cell surface of or to undergo transcytosis across Caco-2 cells or FAE. The selection for transcytosis across both enterocytes and FAE identified three different peptide sequences (CTGKSC, PAVLG and LRVG) with high frequency. CTGKSC and LRVG sequences enhanced phage transport across M-like cells. When polymeric nanoparticles were grafted with the sequences CTGKSC and LRVG, their transport by FAE was significantly enhanced. These peptides could therefore be used to enhance the transport of vaccine-loaded nanoparticles across the intestinal mucosal barrier. [less ▲]

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See detailTargeting nanoparticles to M cells with non-peptidic ligands for oral vaccination
Freichels, Hélène ULg; Fievez, Virginie; Plapied, Laurence et al

Poster (2010, March 18)

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See detailAcylated and unacylatedghrelin binding to membranes and to ghrelin receptor: Towards a better understanding of the underlying mechanisms
Staes, Edith; Absil, Pierre-Antoine; Lins, Laurence ULg et al

in Biochimica et Biophysica Acta - Biomembranes (2010), 1798

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See detailValidation of a method for the quantitation of ghrelin and unacylated ghrelin by HPLC.
Rozet, Eric ULg; Staes, Edith; Ucakar, Bernard et al

in Journal of Pharmaceutical & Biomedical Analysis (2010), 51(3), 633-9

An HPLC/UV method was first optimized for the separation and quantitation of human acylated and unacylated (or des-acyl) ghrelin from aqueous solutions. This method was validated by an original approach ... [more ▼]

An HPLC/UV method was first optimized for the separation and quantitation of human acylated and unacylated (or des-acyl) ghrelin from aqueous solutions. This method was validated by an original approach using accuracy profiles based on tolerance intervals for the total error measurement. The concentration range that achieved adequate accuracy extended from 1.85 to 59.30microM and 1.93 to 61.60microM for acylated and unacylated ghrelin, respectively. Then, optimal temperature, pH and buffer for sample storage were determined. Unacylated ghrelin was found to be stable in all conditions tested. At 37 degrees C acylated ghrelin was stable at pH 4 but unstable at pH 7.4, the main degradation product was unacylated ghrelin. Finally, this validated HPLC/UV method was used to evaluate the binding of acylated and unacylated ghrelin to liposomes. [less ▲]

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See detailTargeting of tumor endothelium by RGD-grafted PLGA-nanoparticles loaded with Paclitaxel
Danhier, Fabienne; Vroman, Benoît; Lecouturier, Nathalie et al

in Journal of Controlled Release (2009), 140(2), 166-173

Paclitaxel (PTX)-loaded PEGylated PLGA-based nanoparticles (NP) have been previously described as more effective in vitro and in vivo than Taxol®. The aim of this study was to test the hypothesis that our ... [more ▼]

Paclitaxel (PTX)-loaded PEGylated PLGA-based nanoparticles (NP) have been previously described as more effective in vitro and in vivo than Taxol®. The aim of this study was to test the hypothesis that our PEGylated PLGA-based nanoparticles grafted with the RGD peptide or RGD-peptidomimetic (RGDp) would target the tumor endothelium and would further enhance the anti-tumor efficacy of PTX. The ligands were grafted on the PEG chain of PCL-b-PEG included in the nanoparticles. We observed in vitro that RGD-grafted nanoparticles were more associated to Human Umbilical Vein Endothelial cells (HUVEC) by binding to αvβ3 integrin than non-targeted nanoparticles. Doxorubicin was also used to confirm the findings observed for PTX. In vivo, we demonstrated the targeting of RGD and RGDp-grafted nanoparticles to tumor vessels as well as the effective retardation of TLT tumor growth and prolonged survival times of mice treated by PTX-loaded RGD-nanoparticles when compared to non-targeted nanoparticles. Hence, the targeting of anti-cancer drug to tumor endothelium by RGD-labeled NP is a promising approach. [less ▲]

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