References of "Riva, Raphaël"
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See detailDesign of polyphosphoester-based drug delivery systems by efficient thiol-ene reaction
Riva, Raphaël ULiege; Vanslambrouck, Stéphanie; Ergül, Zeynep ULiege et al

Poster (2017, May 23)

Thanks to their biocompatibility, biodegradability and their structure similar to natural biomacromolecules, polyphosphoesters (PPE) are appealing polymers for biomedical applications. In contrast to ... [more ▼]

Thanks to their biocompatibility, biodegradability and their structure similar to natural biomacromolecules, polyphosphoesters (PPE) are appealing polymers for biomedical applications. In contrast to polyesters, PPE properties and functionality are easily tuned via the chemical nature of the lateral chains. To enhance the drug loading capacity of PPE-based micelles used as carriers for the delivery of poorly soluble drugs, an efficient strategy to increase the lipophilicity of the PPE block of polyethylene oxide (PEO)-b-PPE amphiphilic copolymers has been investigated. A PEO-b-PPE copolymer bearing pendant vinyl groups along the PPE block was synthesized and then modified by thiol-ene click reaction with thiols bearing either a long linear alkyl chain (dodecyl) or a tocopherol moiety. Ketoconazole was used as model for hydrophobic drugs. Comparison of the loading contents and release profiles with PEO-b-PPE bearing shorter pendant groups is presented evidencing the key role of the structure of the pendant group on the PPE backbone. Finally, the low cytotoxicity of these novel PEO-b-PPE copolymers was also demonstrated. The tocopherol derivative was evidenced as particularly promising for drug delivery systems. [less ▲]

Detailed reference viewed: 34 (3 ULiège)
See detailDesign of new reprocessable shape-memory materials
Defize, Thomas ULiege; Riva, Raphaël ULiege; Thomassin, Jean-Michel ULiege et al

Poster (2017, May 04)

Detailed reference viewed: 10 (2 ULiège)
See detailPhoto-crosslinkable hydrogel for guided periodontal tissue regeneration
Chichiricco, Pauline Marie ULiege; Riva, Raphaël ULiege; Thomassin, Jean-Michel ULiege et al

Poster (2017, May 04)

Periodontitis is an inflammatory disease resulting from the presence of oral bacteria biofilm in periodontal tissue, which destroys the tooth-supporting attachment apparatus. Untreated inflammation can ... [more ▼]

Periodontitis is an inflammatory disease resulting from the presence of oral bacteria biofilm in periodontal tissue, which destroys the tooth-supporting attachment apparatus. Untreated inflammation can spread to the gum tissue and lead, ultimately, to the loosening of the supporting tooth bone, with the risk that the tooth eventually falls. Guided Tissue Regeneration is a technique based on the application of a barrier membrane designed to prevent colonization of the wound space by epithelial cells from soft tissues. Indeed, these cells, characterized by a faster migration and proliferation rate compared to bone and periodontal ligament cells, could interfere with the regeneration process. In previously work Struillou et al. demonstrated the benefit effect of silated hydroxypropylmethylcellulose (Si HMPC)-based hydrogel can act as an efficient physical barrier in periodontal defect. Typically, this material is able to form a 3D network through the condensation of silanoate groups at physiological pH. However, a decrease of gelation time is necessary to assure the stability in peripheral part of the wound. In this project, we developed an injectable photo-crosslinkable membrane based on methacrylated carboxymethyl chitosan (CMCs) and Si HPMC that can be applied as a viscous solution and cured in situ in presence of a photoinitiator system made of riboflavin and triethanolamine. A visible light lamp (λ 420-480 nm), already used in dentistry, was preferred over a UV lamp. The addition of methacrylated polymer increase the stability of the material and increase the mass loss, in order to improve the bioresorption of the membrane. The chemical grafting of methacrylated carboxymethyl chitosan was characterized by 1H NMR and Infrared Spectroscopy. The gel point of the solution was determined by rheology and remained compatible with a clinical application. Moreover, the biocompatibility of this biomaterials was tested using murine cells using two assay: Neutral Red assay and MTT Cell Proliferation Assay. The in vitro tests validate the chemical synthesis in a biological point of view. The irradiation on cells and the direct contact with hydrogel doesn’t have an impact on cells viability. The capability of this material to act as a physical barrier was also evaluated using human gingival fibroblast. The cells were isolated from human gum explant before being put in contact with the hydrogel. After four days of contact no cells invasion was observed in the hydrogel using confocal microscopy. These preliminary results are quite promising for the development of novel injectable systems for Guided Periodontal Regeneration. In the future work, in vivo assays will be performed in Periodontal defect in a canine model. [less ▲]

Detailed reference viewed: 42 (1 ULiège)
See detailThiol-ene reaction: an efficient tool to design polyphosphoester-based drug delivery systems
Riva, Raphaël ULiege; Vanslambrouck, Stéphanie; Ergül, Zeynep ULiege et al

Poster (2017, May 04)

Thanks to their biocompatibility, biodegradability and their structure similar to natural biomacromolecules, polyphosphoesters (PPE) are appealing polymers for biomedical applications. In contrast to ... [more ▼]

Thanks to their biocompatibility, biodegradability and their structure similar to natural biomacromolecules, polyphosphoesters (PPE) are appealing polymers for biomedical applications. In contrast to polyesters, PPE properties and functionality are easily tuned via the chemical nature of the lateral chains. To enhance the drug loading capacity of PPE-based micelles used as carriers for the delivery of poorly soluble drugs, an efficient strategy to increase the lipophilicity of the PPE block of polyethylene oxide (PEO)-b-PPE amphiphilic copolymers has been investigated. A PEO-b-PPE copolymer bearing pendant vinyl groups along the PPE block was synthesized and then modified by thiol-ene click reaction with thiols bearing either a long linear alkyl chain (dodecyl) or a tocopherol moiety. Ketoconazole was used as model for hydrophobic drugs. Comparison of the loading contents and release profiles with PEO-b-PPE bearing shorter pendant groups is presented evidencing the key role of the structure of the pendant group on the PPE backbone. Finally, the low cytotoxicity of these novel PEO-b-PPE copolymers was also demonstrated. The tocopherol derivative was evidenced as particularly promising for drug delivery systems. [less ▲]

Detailed reference viewed: 42 (2 ULiège)
See detailSynthesis of cross-linked poly(HEMA) microparticles in supercritical carbon dioxide for sustained delivery
Caprasse, Jérémie ULiege; Parilti, Rahmet ULiege; Riva, Raphaël ULiege et al

Poster (2017, May 04)

Microgels are micro-sized polymer networks able to swell or shrink depending on the environment. They find applications in many fields such as for environmental purpose or especially in the biomedical ... [more ▼]

Microgels are micro-sized polymer networks able to swell or shrink depending on the environment. They find applications in many fields such as for environmental purpose or especially in the biomedical field for tissue engineering or controlled drug-delivery applications. Indeed, the use of microgels allows a controlled and sustained release of an encapsulated active ingredient (AI), avoiding Burst release. This work aims at reporting on the solvent-free synthesis of well-defined hydrogel microparticles according to a free radical dispersion polymerization of hydroxyethyl methacrylate (HEMA) in supercritical carbon dioxide (scCO2) which confers environmentally benign features to the process2. For that purpose, a dedicated polymer surfactant has been designed by RAFT polymerization, i.e. poly(ethylene oxide-b-heptadecafluorodecyl acrylate) diblock copolymer with a photocleavable group at the junction of both blocks and used as stabilizer for the HEMA dispersion polymerization in scCO2. The synthesis conditions (stabilizer concentration, temperature and CO2 pressure,…) adapted for the in situ encapsulation of an active ingredient have been studied. Then, the photocleavage of the fluorinated block of the polymer stabilizer allows the further swelling of the polyHEMA particles in water and the sustained release of the encapsulated active ingredient through the microgels. This eco-friendly process allowing the formation of well-defined hydrogel particles, showing a sustain release of their content is quite promising for a high scale microparticles production. Microgels are micro-sized polymer networks able to swell or shrink depending on the environment. They find applications in many fields such as for environmental purpose or especially in the biomedical field for tissue engineering or controlled drug-delivery applications. Indeed, the use of microgels allows a controlled and sustained release of an encapsulated active ingredient (AI), avoiding Burst release. [less ▲]

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See detailBioreducible cross-linked core polymer micelles enhance in vitro activity of methotrexate in breast cancer cells
Gulfam, Muhammad ULiege; Matini, Teresa; Monteiro, Patrícia F et al

in Biomaterials Science (2017), 5(3), 532-550

Polymer micelles have emerged as promising carriers for controlled release applications, however, several limitations of micelle-based drug delivery have also been reported. To address these issues, we ... [more ▼]

Polymer micelles have emerged as promising carriers for controlled release applications, however, several limitations of micelle-based drug delivery have also been reported. To address these issues, we have synthesized a functional biodegradable and cytocompatible block copolymer based on methoxypoly (ethyleneglycol)-b-poly(ε-caprolactone-co-α-azido-ε-caprolactone) (mPEG-b-poly(εCL-co-αN3εCL)) as a precursor of reduction sensitive core-crosslinked micelles. The synthesized polymer was formulated as micelles using a dialysis method and loaded with the anti-inflammatory and anti-cancer drug metho- trexate (MTX). The micellar cores were subsequently crosslinked at their pendent azides by a redox- responsive bis(alkyne). The size distributions and morphology of the polymer micelles were assessed using dynamic light scattering (DLS) and transmission electron microscopy, and drug release assays were performed under simplified (serum free) physiological and reductive conditions. Cellular uptake studies in human breast cancer cells were performed using Oregon-green loaded core-crosslinked micelles. The MTX-loaded core-crosslinked micelles were assessed for their effects on metabolic activity in human breast cancer (MCF-7) cells by evaluating the reduction of the dye MTT 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The apoptosis inducing potential of MTX-loaded core-crosslinked micelles was analysed using Hoechst/propidium iodide (PI) and annexin-V/PI assays. The data from these experi- ments indicated that drug release from these cross-linked micelles can be controlled and that the redox- responsive micelles are more effective carriers for MTX than non-crosslinked analogues and the free drug in the cell-lines tested. [less ▲]

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See detailReversible TAD chemistry as a convenient tool for the design of (re)processable PCL-based shape-memory materials
Defize, Thomas ULiege; Riva, Raphaël ULiege; Thomassin, Jean-Michel ULiege et al

in Macromolecular Rapid Communications (2017), 38(1), 1600517

A chemically cross-linked but remarkably (re)processable shape-memory polymer (SMP) is designed by cross-linking poly(ε -caprolactone) (PCL) stars via the efficient triazolinedione click chemistry, based ... [more ▼]

A chemically cross-linked but remarkably (re)processable shape-memory polymer (SMP) is designed by cross-linking poly(ε -caprolactone) (PCL) stars via the efficient triazolinedione click chemistry, based on the very fast and reversible Alder– ene reaction of 1,2,4-triazoline-3,5-dione (TAD) with indole compounds. Typically, a six-arm star-shaped PCL function- alized by indole moieties at the chain ends is melt-blended with a bisfunctional TAD, directly resulting in a cross-linked PCL-based SMP without the need of post-curing treatment. As demonstrated by the stress relaxation measurement, the labile character of the TAD–indole adducts under stress allows for the solid-state plasticity reprocessing of the permanent shape at will by compression molding of the raw cross-linked material, while keeping excellent shape-memory properties. [less ▲]

Detailed reference viewed: 55 (24 ULiège)
See detailOrganocatalytic ring-opening polymerization towards polyphosphoesters
Clément, Benoit; Vanslambrouck, Stépanie; Carion, Stéphan ULiege et al

Conference (2016, September 13)

Hydrolytically degradable and biocompatible aliphatic polyesters are widely applied for biomedical applications as implants, scaffolds for tissue engineering and, finally, as nanocarriers for drug ... [more ▼]

Hydrolytically degradable and biocompatible aliphatic polyesters are widely applied for biomedical applications as implants, scaffolds for tissue engineering and, finally, as nanocarriers for drug delivery. Aliphatic phophoesters, known since the pioneering work of S. Penczek in the 70’s, exhibit the same properties of hydrolytic degradability and biocompatibility and are thus more and more studied for biomedical applications as well. In the field of materials, anti-fire properties opens up new perspectives. The difference between polyesters and polyphosphoesters in terms of synthesis and properties will be highlighted. Polyphosphosphoesters are synthesized by step-growth and chain growth polymerization. When these polyphosphoesters are synthesized by ring-opening polymerization of cyclic phosphoesters, organocatalysts turned out to be very efficient compared to coodination processes. The last part of the talk will deal with te implementation of ROP of cyclic phosphates towards a series of amphiphilic PEO-block-polyphosphate copolymers of tailored hydrophobicity depending on the length of the lateral alkyl group. These polymers are able to self assemble into nanoparticles by direct dissolution in water, thus in the absernce of any organic solvent. The so-obtained micelles were studied by a set of techniques (Pyrene Fluorescence, Dynamic Light Scattering, Tensiometry). Finally, the influence of the hydrophobicity of the polyphosphate block of the micelle on the encapsulation and the release of a model drug was investigated. [less ▲]

Detailed reference viewed: 81 (12 ULiège)
See detailPolyphosphoester containing amphiphilic block copolymers as drug nanocarriers
Ergül, Zeynep ULiege; Vanslambrouck, Stéphanie; Thiry, Justine ULiege et al

Poster (2016, September 12)

The design of drug delivery systems often requires biodegradable and biocompatible materials that allow safe retention and controlled release of the drug. In this respect, supramolecularly self-assembled ... [more ▼]

The design of drug delivery systems often requires biodegradable and biocompatible materials that allow safe retention and controlled release of the drug. In this respect, supramolecularly self-assembled amphiphilic block copolymers into spherical micelles are appropriate carriers for poorly soluble drugs. In that framework, we have designed novel functional poly(ethylene oxide)-b-polyphosphoester amphiphilic block copolymers able to cross-linked under UV and degrade in response to a reduction of the pH from neutral conditions. Therefore, an unsaturated alkene side-chain was introduced on the cyclic phosphate monomer according to a one-step reaction followed by its organocatalyzed polymerization initiated by a poly(ethylene oxide) macroinitiator. After self-assembly into water, the micelles were cross-linked by UV irradiation. Then, these cross-linked micelles have been loaded by doxorubicin, i.e. a drug used in cancer therapy. We observed that the doxorubicin loading increased with the number of double bonds on the polyphosphate block of non-cross-linked micelles. This diblock amphiphilic copolymer bearing pendant unsaturations appears thus particularly promising candidate to build micellar drug delivery systems for intravenous injection. [less ▲]

Detailed reference viewed: 39 (3 ULiège)
See detailPolyphosphoesters as a new platform for the design of particulate drug delivery systems
Vanslambrouck, Stéphanie; Ergul Yilmaz, Zeynep; Debuigne, Antoine ULiege et al

Conference (2016, June)

Thanks to their biocompatibility and degradability properties, polyphosphates are appealing polymers for biomedical applications. In contrast to aliphatic polyesters, such as poly(ε-caprolactone) and poly ... [more ▼]

Thanks to their biocompatibility and degradability properties, polyphosphates are appealing polymers for biomedical applications. In contrast to aliphatic polyesters, such as poly(ε-caprolactone) and poly(lactide), the pentavalency of the phosphorus atom allows the easy modification of the polyphosphate properties by simply adjusting the nature, the length and the functionality of the polyphosphate pendant groups. Therefore, macromolecular engineering of polyphosphoesters was applied to design well-defined architectures and functionalities adapted to drug nanocarriers. In a first approach, amphiphilic block copolymers are synthesized by organo-catalyzed ring-opening polymerization process for the synthesis of a range of PEO-b-polyphosphate bearing various pendant groups. Post-polymerization thiol-ene click reactions preformed on PEO-b-polyphosphate copolymers was also investigated to improve the hydrophobicity of the polyphosphate. The self-assembly of these PEO-b-polyphosphate copolymers into micelles was investigated, particularly, the effect of the nature of the polyphosphate pendant groups (i) on the micelles characteristics, (ii) on the encapsulation of a poorly soluble drug and (iii) on the drug release profile. The toxicity of the different amphiphilic block copolymers was also evaluated by live/dead cell viability assays. In a second approach, double hydrophilic copolymers based on polyphosphoesters have been used as templating agent for the synthesis of calcium carbonate particles. Indeed, the use of such microparticles is becoming more and more attractive in many fields especially for biomedical applications for which fine tuning of size, morphology and crystalline form of CaCO3 particles is crucial. Although some structuring compounds, like hyaluronic acid, give satisfying results, the control of the particle structure still has to be improved. To this end, we evaluated the CaCO3 structuring capacity of the well-defined double hydrophilic block copolymers composed of poly(ethylene oxide) and of a polyphosphoester segment with affinity for calcium like poly(phosphotriester)s bearing pendant carboxylic acids or poly(phosphodiester)s with a negatively charged oxygen atom on each repeating monomer unit. [less ▲]

Detailed reference viewed: 203 (15 ULiège)
See detailPolyphosphoester containing amphiphilic block copolymers as drug nanocarriers
Yilmaz-Ergül, Zeynep ULiege; Vanslambrouck, Stéphanie; Thiry, Justine ULiege et al

Poster (2016, May 23)

The design of drug delivery systems (DDS) often requires biodegradable and biocompatible materials that allow safe retention and controlled release of the drug. In this respect, poly(ethylene oxide)-b ... [more ▼]

The design of drug delivery systems (DDS) often requires biodegradable and biocompatible materials that allow safe retention and controlled release of the drug. In this respect, poly(ethylene oxide)-b-polyphosphoester amphiphilic block copolymers are known to self-assemble into polymer micelles when placed in water are appropriate drug carriers. In this work, an unsaturated alkene side-chain was introduced on the cyclic phosphate monomer according to a one-step reaction followed by its organocatalyzed polymerization initiated by a poly(ethylene oxide) macroinitiator. After self-assembly into water, the micelles were cross-linked by UV irradiation. Then, these cross-linked micelles have been loaded by doxorubicin, which is a drug to use in cancer therapy. We observed that the doxorubicin loading increased with the number of double bonds on the polyphosphate block of non-cross-linked micelles. This diblock amphiphilic copolymer bearing pendant unsaturations appears thus particularly promising candidate to build micellar drug delivery systems for intravenous injection. [less ▲]

Detailed reference viewed: 77 (8 ULiège)
See detailRecyclable shape-memory materials based on photo- or thermo-reversible reactions
Defize, Thomas ULiege; Riva, Raphaël ULiege; Thomassin, Jean-Michel ULiege et al

Poster (2016, February 16)

Shape-memory polymers (SMPs) are remarkable materials able to switch from a stressed deformed state (temporary shape) to their initial relaxed state (permanent shape) by the application of a stimulus ... [more ▼]

Shape-memory polymers (SMPs) are remarkable materials able to switch from a stressed deformed state (temporary shape) to their initial relaxed state (permanent shape) by the application of a stimulus, such as heat or light. Typically, the shape-memory property is generally observed for chemically or physically cross-linked polymers that exhibit an elastomeric behavior above a phase transition, e.g. glass or melting transition. As an example, cross-linked semi-crystalline poly(ε-caprolactone) (PCL) is widely studied for the development of SMPs. As most of SMPs are irreversibly cross-linked material, their reprocessing is impossible preventing any recycling. Thereby, reversible reactions, allowing the formation/cleavage of the network, raise tremendous interest for the development of new SMPs. Recently, we reported the preparation reversibly cross-linked PCL-based SMP using the Diels-Alder (DA) reaction between furan and maleimide end-groups of 4-arm star-shaped PCL, well-known to create reversible bonds. After implementation, this shape-memory material was demonstrated to be recyclable, and was characterized by excellent fixity and recovery before and after recycling experiments. However, the relatively low retro DA temperature of the furan-maleimide adducts led to an inelastic deformation during shape-memory tensile cycles. In order to get rid of this drawback, an alternative approach was investigated. The substitution of the DA reaction by a photo-reversible reaction, typically the photo-induced (2+2) cycloaddition of coumarins, was proposed to prepare cross-linked PCL matrix presenting one-way and two-way memory properties, since photolabile adducts are supposed to be stable during shape-memory tensile cycles. [less ▲]

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See detailComprehensive study of the thermo-reversibility of Diels-Alder based PCL polymer networks
Defize, Thomas ULiege; Thomassin, Jean-Michel ULiege; Alexandre, Michaël et al

in Polymer (2016), 84

Chemical crosslinking is an efficient tool to improve or impart new properties to conventional polymers. Especially, crosslinking imparts remarkable shapeememory properties to poly-ε-caprolactone (PCL ... [more ▼]

Chemical crosslinking is an efficient tool to improve or impart new properties to conventional polymers. Especially, crosslinking imparts remarkable shapeememory properties to poly-ε-caprolactone (PCL) materials. Nevertheless, the processing of networks is often tricky due to infusibility and insolubility of cross-linked chains. Therefore, the synthesis of PCL networks including thermo-reversible crosslinks based on (retro)-Diels-Alder (DA) reaction were developed to allowpreserving the melt-processing while keeping the required mechanical properties below the melting point. This paper aims at studying in depth, such thermo-dependent network formation and stability. Besides conventional swelling experi- ments, Raman spectroscopy was revealed as a powerful tool to follow the formation of the DA adduct during the crosslinking. In combination with rheological measurements, we were able to determine the most appropriate temperatures to form the network (DA crosslinking) and to process it (retro-DA re- action) without degradation of the material. [less ▲]

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See detailCore cross-linked micelles of polyphosphoester containing amphiphilic block copolymers as drug nanocarriers
Ergül, Zeynep ULiege; Vanslambrouck, Stéphanie; Cajot, Sébastien et al

in RSC Advances (2016), 6(48), 42081-42088

Poly(ethylene oxide)-b-polyphosphoester amphiphilic block copolymers are known to self-assemble into polymer micelles when dissolved into water. This work aims at reporting on the improvement of the ... [more ▼]

Poly(ethylene oxide)-b-polyphosphoester amphiphilic block copolymers are known to self-assemble into polymer micelles when dissolved into water. This work aims at reporting on the improvement of the stability of the micelles at high dilution by crosslinking the hydrophobic polyphosphoester micellar core. Typically, an unsaturated alkene side-chain was introduced on the cyclic phosphate monomer according to a one-step reaction followed by its organocatalyzed polymerization initiated by a poly(ethylene oxide) macroinitiator. This strategy avoids the use of any organometallic compounds in order to facilitate the purification and meet the stringent requirements of biomedical applications. After self-assembly into water, the micelles were cross-linked by simple UV irradiation. These cross-linked micelles have then been loaded by doxorubicin to evaluate their potential as drug nanocarriers and monitor the impact of crosslinking on the release profile. [less ▲]

Detailed reference viewed: 45 (17 ULiège)