References of "Freichels, Hélène"
     in
Bookmark and Share    
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 17 (3 ULg)
Full Text
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)

Detailed reference viewed: 38 (6 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 52 (8 ULg)
Full Text
See detailPréparation de nouveaux copolymères amphiphiles mannosylés d'architecture greffée et caractérisation par QCM-D
Freichels, Hélène ULg; Broze, Guy; Alaimo, David ULg et al

Conference (2009, October 14)

Durant les dernières décennies, le domaine pharmaceutique s’est intéressé aux micelles et nanoparticules polymères celles-ci pouvant être utilisées comme vecteurs à libération contrôlée. Dans ce domaine ... [more ▼]

Durant les dernières décennies, le domaine pharmaceutique s’est intéressé aux micelles et nanoparticules polymères celles-ci pouvant être utilisées comme vecteurs à libération contrôlée. Dans ce domaine, des copolymères amphiphiles combinant le poly(oxyde d’éthylène) (POE), polymère possédant des propriétés répulsives vis-à-vis des protéines plasmiques, et la poly-epsilon-caprolactone (PCL), un polyester aliphatique, polymère hydrophobe biocompatible et biodégradable permettant l’incorporation d’un principe actif hydrophobe, sont d’excellents candidats pour cette d’application. Jusqu’à présent, ce type de copolymère amphiphile principalement étudié est d’architecture linéaire. Récemment, notre laboratoire a développé une stratégie permettant la préparation de nouveaux copolymères greffés, composés d’un squelette principal de PCL et de greffons de POE. De plus, des agents de ciblage peuvent être introduits à l’extrémité du POE de ces copolymères amphiphiles, faisant de ceux-ci des candidats idéaux comme vecteur de troisième génération, permettant un ciblage spécifique au sein même de l’organisme. Le mannose est un agent intéressant, car il est reconnu à la surface des cellules dendritiques. Dans ce travail, la préparation de copolymères greffés fonctionnalisés par du mannose est décrite. La présence de mannose à la surface des micelles a d’abord été mise en évidence par test ELLA (Enzyme Linked Lectin Assay). Ensuite une étude plus approfondie a été réalisée par QCM-D (Microbalance à Cristal de Quartz avec Dissipation). Cette technique originale permet de mettre en évidence l’interaction entre la lectine immobilisée sur la surface du cristal de la microbalance et le mannose exposés à la périphérie des micelles du copolymère. [less ▲]

Detailed reference viewed: 142 (13 ULg)
Full Text
See detailMannosylated amphiphilic and degradable PEO-b-PCL copolymers for drug delivery systems: preparation and sugar availability characterizations
Freichels, Hélène ULg; Imberty, Anne; Auezély-Velty, Rachel et al

Poster (2009, May 14)

Over the last decade, polymer micelles and nanoparticles attracted an increasing interest in pharmaceutical research because they can be used as efficient drug delivery systems. In this field, amphiphilic ... [more ▼]

Over the last decade, polymer micelles and nanoparticles attracted an increasing interest in pharmaceutical research because they can be used as efficient drug delivery systems. In this field, amphiphilic copolymers combining poly(ethylene oxide) and aliphatic polyester (such as poly(ε-caprolactone) (PCL) or polylactide (PLA)) are particularly of interest because (i) PEO has unique protein- repellent properties and thus provides a stealth behaviour to the drug carriers and (ii) aliphatic polyesters are biocompatible and biodegradable hydrophobic matrices well-suited for the incorporation of an hydrophobic drug. By end-capping the hydrophilic segment by a targeting moiety so that they may interact with membrane receptors, the biodistribution of polymeric micelles and nanoparticles stabilized with this copolymer can be modulated and can induce specific cellular uptake by receptor-mediated endocytosis. One class of interesting targeting agent is the saccharides, in particular the mannose, because of its specific interaction with mannose receptor, which are found on peripheral and bone marrow macrophages, dendritic cells and sinusoidal liver cells. In this study, the reductive amination reaction is use to attach this targeting agent. After optimisation of the reaction with amino fluorescein, a model amine, mannosylated copolymer of PEO and PCL has been prepared. The surface availability of the saccharide upon the micelles in aqueous phosphate buffer was then assessed by DLS through binding with the protein Concanavalin A (ConA), a known mannose receptor. The interactions between the Bcla lectin and the mannosylated micelles have then been studied by Isothermal Titration Calorimetry (ITC) and the thermodynamic parameters have been obtained. This polymer is particularly useful for the stabilization of PLGA nanoparticles with the goal to target M cells for oral vaccination. [less ▲]

Detailed reference viewed: 68 (10 ULg)
Full Text
Peer Reviewed
See detailLight induced functionalization of PCL-PEG block copolymers for the covalent immobilization of biomolecules
Pourcelle, Vincent; Freichels, Hélène ULg; Stoffelbach, François et al

in Biomacromolecules (2009), 10(4), 966-974

Functionalized poly-ε-caprolactone-block-polyethyleneglycol (PCL-PEG) amphiphilic copolymers were prepared to be constituents of nanocarriers used for the targeting of specific cells. Hence, we conceived ... [more ▼]

Functionalized poly-ε-caprolactone-block-polyethyleneglycol (PCL-PEG) amphiphilic copolymers were prepared to be constituents of nanocarriers used for the targeting of specific cells. Hence, we conceived a smooth and simple photografting methodology on these copolymers using a bifunctional molecular clip (O-succinimidyl-4-(p-azido-phenyl)butanoate). We prepared PCL-PEGs with pendent N-hydroxysuccinimide esters and studied the grafting with 3H-lysine, which radioactivity was counted by LSC. Several parameters were investigated, such as behavior of homopolymers, initial concentrations, irradiation, and incubation durations. Evidences of a “PEG directed photografting” are discussed and this selectivity could be improved by a selective solvent technique. The photografting on different PCL-PEGs revealed a dependency of the rates to the crystallinity of the copolymers. Several controls by SEC, DLS, and TEM of the treated copolymers were realized. Lastly, the coupling of α-d-mannopyranoside ligand was performed, reaching amounts of 5400 nmol/g of PCL-PEG. This derivatized PCL-PEG enters in the preparation of nanocarriers used for the targeting of antigen presenting cells. [less ▲]

Detailed reference viewed: 39 (4 ULg)
Full Text
Peer Reviewed
See detailPolyester nanoparticles presenting mannose residues : toward the development of new vaccine delivery systems combining biodegradability and targeting properties
Rieger, Jutta ULg; Freichels, Hélène ULg; Imberty, Anne et al

in Biomacromolecules (2009), 10(3), 651-657

We report the synthesis of fully biodegradable polymeric nanoparticles presenting mannose residues at their surface and their interaction with lectins. A simple and versatile method was used to reach the ... [more ▼]

We report the synthesis of fully biodegradable polymeric nanoparticles presenting mannose residues at their surface and their interaction with lectins. A simple and versatile method was used to reach the surface functionalization of poly(d,l-lactic acid) (PLA) nanoparticles by mannose moieties: It consists in using an amphiphilic mannosylated poly(ethylene oxide)-b-poly(-caprolactone) (PEO-b-PCL) diblock copolymer as a bioresorbable surface modifier in a simple nanoprecipitation-evaporation procedure. The size and zeta potential of the nanoparticles were found to depend on the molar copolymer/PLA ratio, demonstrating the influence of the copolymer on the formation of the nanoparticles. The bioavailability of the mannose residues as specific recognition sites on the nanoparticle surface could be demonstrated by a modified enzyme-linked lectin assay (ELLA) using biotin-labeled lectins which interact specifically with α-d-mannopyrannoside derivatives. Besides specific interaction by lectin−mannose complex formation, nonspecific adsorption of the proteins on the nanoparticle surface was observed. These results were fully supported by isothermal titration calorimetry experiments which suggested that the balance between specific and nonspecific interactions can be controlled by the amount of glycosylated polymer used for the preparation of the nanoparticles. Such nanoparticles are expected to be specifically recognized by mannose receptors, which are highly expressed in cells of the immune system. The targeting properties of these carrier systems combined with their potential adjuvant effects due to their size in the range of 200−300 nm make them attractive candidates as vaccine delivery systems. [less ▲]

Detailed reference viewed: 58 (7 ULg)
Full Text
See detailFunctional amphiphilic and degradable copolymers for drug delivery systems
Freichels, Hélène ULg; Pourcelle, Vincent; Plapied, Laurence et al

Poster (2008, December 18)

Detailed reference viewed: 23 (4 ULg)
See detailNovel amphiphilic degradable copolymers for drug deivery systems
Van Butsele, Kathy; Freichels, Hélène ULg; Rieger, Jutta et al

Poster (2007, August 31)

Detailed reference viewed: 15 (1 ULg)
Full Text
Peer Reviewed
See detailPEGylated PLGA-based nanoparticles targeting M cells for oral vaccination
Garinot, Marie; Fievez, Virginie; Pourcelle, Vincent et al

in Journal of Controlled Release (2007), 120(3), 195-204

To improve the efficiency of orally delivered vaccines, PEGylated PLGA-based nanoparticles displaying RGD molecules at their surface were designed to target human M cells. RGD grafting was performed by an ... [more ▼]

To improve the efficiency of orally delivered vaccines, PEGylated PLGA-based nanoparticles displaying RGD molecules at their surface were designed to target human M cells. RGD grafting was performed by an original method called "photografting" which covalently linked RGD peptides mainly on the PEG moiety of the PCL-PEG, included in the formulation. First, three non-targeted formulations with size and zeta potential adapted to M cell uptake and stable in gastro-intestinal fluids, were developed. Their transport by an in vitro model of the human Follicle associated epithelium (co-cultures) was largely increased as compared to mono-cultures (Caco-2 cells). RGD-labelling of nanoparticles significantly increased their transport by co-cultures. due to interactions between the RGD ligand and the I intregrins detected at the apical surface of co-cultures. In vivo studies demonstrated that RGD-labelled nanoparticles particularly concentrated in M cells. Finally, ovalbumin-loaded nanoparticles were orally administrated to mice and induced an IgG response, attesting antigen ability to elicit an immune response after oral delivery. [less ▲]

Detailed reference viewed: 62 (5 ULg)