References of "Guégan, Philippe"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailPoly(N-methylvinylamine)-based copolymers for improved gene transfection
Dréan, Mathilde; Debuigne, Antoine ULiege; Jérôme, Christine ULiege et al

in Macromolecular Bioscience (2018), 18(4), 1700353

Poly(N-methylvinylamines) with secondary amines can form complexes with plasmid DNA (pDNA) and provide transfection efficiency in HeLa cells in the same order as linear polyethyleneimine but with higher ... [more ▼]

Poly(N-methylvinylamines) with secondary amines can form complexes with plasmid DNA (pDNA) and provide transfection efficiency in HeLa cells in the same order as linear polyethyleneimine but with higher cell viability. Chemical modifications of poly(N-methylvinylamine) backbones are performed to further improve transfection efficiency while maintaining low degree of cytotoxicity. In a first type of polymer, primary amino groups are incorporated via a copolymerization strategy. In a second one, primary amino and imidazole groups are incorporated also via a copolymerization strategy. In a third one, secondary amino groups are substituted with methylguanidine functions through a postpolymerization reaction. Thus, novel polymers of various molecular masses are synthesized, characterized, and their interaction with pDNA studied. Then, their transfection efficiency and cytotoxicity are tested in HeLa cells. Two polymethylvinylamine-based copolymers, one containing 20% of imidazole moieties and another one composed of 12% of guanidinyl units allow remarkable transfection efficiency of HeLa, pulmonary (16HBE), skeletal muscle (C2C12), and dendritic (DC2.4) cells. Overall, this work thus identifies new promising DNA carriers and chemical modifications that improve the transfection efficiency while maintaining low degree of cytotoxicity. [less ▲]

Detailed reference viewed: 51 (11 ULiège)
Full Text
See detailImprovement in or relating to organic material
Debuigne, Antoine ULiege; Dréan, Mathilde; Guégan, Philippe et al

Patent (2017)

The present invention provides polyplex comprising: (a) at least one polymer of formula (I) comprising at least one set of repeating units of formula: and wherein for each set of repeating units R 1 ... [more ▼]

The present invention provides polyplex comprising: (a) at least one polymer of formula (I) comprising at least one set of repeating units of formula: and wherein for each set of repeating units R 1 represents either a hydrogen atom or a straight or branched chain alkyl group having from 1 to 20 carbon atoms and R 2 represents a straight or branched chain alkyl group having from 1 to 20 carbon atoms, wherein n and m each represent an integer of from 1 to 5000, wherein the sum of n and m is from 10 to 250 when R 1 represents a hydrogen atom and when the polymer of formula (I) contains only one set of repeating units; and (b) at least one nucleic acid having improved transfection efficient and reduced cytotoxicity; a method for preparing a polyplex; a method for preparing the polymer of formula (I) for use in the polyplex; a method for transferring at least one nucleic acid into a cell and a pharmaceutical composition comprising the polyplex and an adjuvant; use of a polyplex or of a pharmaceutical composition according to the invention in transferring at least one nucleic acid into a cell; and use of a polymer of formula (I) as defined above in transferring of at least one nucleic acid into a cell.. To be accompanied when published by Figure 1 of the accompanying drawings. [less ▲]

Detailed reference viewed: 19 (6 ULiège)
See detailWell-defined polyvinylamine-based copolymers: synthesis by organometallic-mediated radical polymerization and use in gene transfection
Debuigne, Antoine ULiege; Dréan, Mathilde; Detrembleur, Christophe ULiege et al

Conference (2017, August 22)

Polyvinylamine (PVAm) presents valuable properties like affinity for many supports, pH responsiveness, metal binding capacity, polyelectrolytes complexation, and is used in various applications including ... [more ▼]

Polyvinylamine (PVAm) presents valuable properties like affinity for many supports, pH responsiveness, metal binding capacity, polyelectrolytes complexation, and is used in various applications including coatings, water purification or gas membrane separation. PVAm is commonly prepared by free radical polymerization of N-vinyl monomers followed by deprotection and release of the masked amino functions. However, examples of controlled synthesis of polyvinylamine-based copolymers are scarce because of the high reactivity of the propagating radicals deriving from non-conjugated N-vinyl monomers due to the lack of resonance stabilization. The present communication aims at reporting an efficient platform for producing tailor-made PVAms via organometallic-mediated radical polymerization (OMRP) of N-vinylacetamides followed by hydrolysis of the pendent amide moieties. In this case, cobalt(II) acetylacetonate was successfully used as controlling agent. The synthesis of a series of well-defined homopolymers, statistical and block copolymers with pendent primary and/or secondary amines having low dispersities, predictable molar masses and precise compositions, will be described. Finally, we will discuss the possible use of these polyvinylamine-containing copolymers as gene transfection agents. Some of them demonstrated high DNA transfection level in combination with high cell viability. [less ▲]

Detailed reference viewed: 158 (12 ULiège)
Full Text
Peer Reviewed
See detailUse of primary and secondary polyvinylamines for efficient gene transfection
Dréan, Mathilde; Debuigne, Antoine ULiege; Gonçalves, Christine et al

in Biomacromolecules (2017), 18(2), 440-441

Gene transfection with polymeric carrier remains a challenge, particularly high transfection levels combined with low toxicity are hard to achieve. We herein revisit polyvinylamines, an old and neglected ... [more ▼]

Gene transfection with polymeric carrier remains a challenge, particularly high transfection levels combined with low toxicity are hard to achieve. We herein revisit polyvinylamines, an old and neglected family of cationic polymers. They can be readily obtained by controlled hydrolysis of polyvinylamides prepared through (controlled) radical polymerization. A series of tailor-made and well-defined polyvinylamines bearing primary amino groups, and poly(N- methylvinylamine) bearing secondary amines, were evaluated for the transfection of cells with pDNA as a function of their molar mass, molar mass distribution and degree of deacetylation. Unexpected high transfection levels, in combination with low cytotoxicity were recorded for both series. Surprisingly, a great impact of the molar mass was observed for the primary amine polyvinylamine series, whereas the results were mostly independent on molar mass or dispersity for the polymer bearing secondary amine. It was further established that a certain percentage of acetamide groups increased the transfection level, while maintaining low cytotoxicity. These results highlight for the first time the real potential of polyvinylamines as gene carriers, and make these polymers very attractive for further development in gene therapy. [less ▲]

Detailed reference viewed: 46 (20 ULiège)
Full Text
Peer Reviewed
See detailControlled synthesis of poly(vinylamine)-based copolymers by organometallic-mediated radical polymerization
Dréan, Mathilde ULiege; Guégan, Philippe; Detrembleur, Christophe ULiege et al

in Macromolecules (2016), 49(13), 4817-4827

iving/controlled polymerization methods have enabled the synthesis of numerous (co)polymers with defined compositions and architectures. However, the precision design of poly(vinylamine)-based copolymers ... [more ▼]

iving/controlled polymerization methods have enabled the synthesis of numerous (co)polymers with defined compositions and architectures. However, the precision design of poly(vinylamine)-based copolymers remains challenging despite their extensive use in various fields of applications and the clear benefits to finely tune their properties. Here, we report on a two-step strategy for the synthesis of tailor-made poly(vinylamine) derivatives through the organometallic- mediated radical (co)polymerization (OMRP) of N-vinyl- acetamide and/or N-methylvinylacetamide followed by acid hydrolysis of the acetamide groups. A series of well-defined homopolymers as well as statistical and block copolymers with pendant primary and/or secondary amines having controlled molar masses, compositions, and low dispersities were produced accordingly. The reactivity ratios of the comonomers as well as the composition drift along the chain were determined in order to have a precise idea of the polymer structures. These advances represent a significant step toward an efficient platform for synthesis of this important class of amino group-containing (co)polymers. [less ▲]

Detailed reference viewed: 58 (16 ULiège)
See detailSynthesis of novel well-defined poly(vinylamine)-based copolymers by controlled polymerization
Dréan, Mathilde; Guégan, Philippe; Detrembleur, Christophe ULiege et al

Poster (2016, May 23)

Metal binding, pH sensitivity and polyelectrolytes complexation are key characteristics of amine-containing polymers. Among them, poly(vinylamine)s presenting high amine densities are particularly useful ... [more ▼]

Metal binding, pH sensitivity and polyelectrolytes complexation are key characteristics of amine-containing polymers. Among them, poly(vinylamine)s presenting high amine densities are particularly useful in many fields such as coatings , water purification and gas membrane separation. The properties of such polymers strongly depend on the nature of the amines and can thus be adjusted by incorporating different types of amines along the backbone. In this perspective, we developed a strategy for synthesizing poly(vinylamine)-based (co)polymers containing primary and secondary amines as well as imidazole moieties in predictable proportions. First, radical (co)polymerizations of N-vinylacetamide, N-methylvinylacetamide and vinylimidazole were performed followed by deprotection of the amine functions via acidic hydrolysis of the pendant amides. We determined the reactivity ratios of each comonomer pairs and developed the corresponding Skeist’s model, allowing the prediction of the copolymer compositions and distributions. Following this straightforward approach, novel amine-containing copolymers with predictable and precise compositions were made available and should contribute in the future to the development of the above-mentioned applications. [less ▲]

Detailed reference viewed: 21 (2 ULiège)
See detailSynthesis of novel poly(vinylamine)-based copolymers with controlled compositions
Dréan; Guégan, Philippe; Detrembleur, Christophe ULiege et al

Poster (2016, May 23)

Metal binding, pH sensitivity and polyelectrolytes complexation are key characteristics of amine-containing polymers. Among them, poly(vinylamine)s presenting high amine densities are particularly useful ... [more ▼]

Metal binding, pH sensitivity and polyelectrolytes complexation are key characteristics of amine-containing polymers. Among them, poly(vinylamine)s presenting high amine densities are particularly useful in many fields such as coatings , water purification and gas membrane separation. The properties of such polymers strongly depend on the nature of the amines and can thus be adjusted by incorporating different types of amines along the backbone. In this perspective, we developed a strategy for synthesizing poly(vinylamine)-based (co)polymers containing primary and secondary amines as well as imidazole moieties in predictable proportions. First, radical (co)polymerizations of N-vinylacetamide, N-methylvinylacetamide and vinylimidazole were performed followed by deprotection of the amine functions via acidic hydrolysis of the pendant amides. We determined the reactivity ratios of each comonomer pairs and developed the corresponding Skeist’s model, allowing the prediction of the copolymer compositions and distributions. Following this straightforward approach, novel amine-containing copolymers with predictable and precise compositions were made available and should contribute in the future to the development of the above-mentioned applications. [less ▲]

Detailed reference viewed: 48 (5 ULiège)
See detailPolyvinylamine based copolymers for gene delivery
Dréan, Mathilde; Debuigne, Antoine ULiege; Guégan, Philippe et al

Conference (2016, March 16)

Gene delivery consists in the insertion of functional genes in the cells of a patient in order to correct a specific genetic defect responsible for diseases. The synthetic vehicles attract more and more ... [more ▼]

Gene delivery consists in the insertion of functional genes in the cells of a patient in order to correct a specific genetic defect responsible for diseases. The synthetic vehicles attract more and more attention today due to their lower immunogenicity, ability to carry larger DNA loads and their possible large scale production. The use of nano-complexes between polycations and the negatively charged DNA molecules is the most widespread polymer-based transfection mode. Polyethyleneimine (PEI) is the most common and efficient non-viral gene transfer agent but some alternatives which can improve transfection efficacy and low toxicities are under researches. The polyvinylamine (PVAm), another polycation with a high charge density, has been investigated but these studies are limited to unmodified PVAm chains. In this project, we exploit the latest progress in the field of controlled radical polymerization (CRP) for designing well-defined and advanced functional PVAm derivatives devoted to gene therapy application and establish a structure-gene transfer activity relationship. Incorporation of appropriate pH-responsive moieties, like the vinylimidazole, able to play the role of “protons pumps” as well as introduction of biocompatible segments in the PVAm will be considered in order to facilitate the release of nucleic acids chains in the cytoplasm and improve the biocompatibility of the carrier, respectively. [less ▲]

Detailed reference viewed: 41 (6 ULiège)
Full Text
Peer Reviewed
See detailFar beyond primary poly(vinylamine)s through free radical copolymerization and amide hydrolysis
Dréan, Mathilde ULiege; Guégan, Philippe; Jérôme, Christine ULiege et al

in Polymer Chemistry (2016), 7(1), 69-78

Due to their affinity for many supports, their pH responsiveness, metal binding capacity and polyelectro- lyte complexation, poly(vinylamine) derivatives have attracted attention for many applications ... [more ▼]

Due to their affinity for many supports, their pH responsiveness, metal binding capacity and polyelectro- lyte complexation, poly(vinylamine) derivatives have attracted attention for many applications including coatings, water purification, or gas membrane separation. Nevertheless, most of them possess only pendant primary amines despite the possible benefits of incorporating different amino groups along the chain. In this work, a straightforward and scalable synthesis route towards polymers bearing primary and secondary amines, as well as imidazole groups, is reported. The general strategy relies on the radical copolymerization of different vinylamides and vinyl imidazoles followed by the hydrolysis of the resulting poly(vinylamide) derivatives. Binary and ternary free radical copolymerizations of N-vinylacetamide (NVA), N-methyl vinylacetamide (NMVA) and 1-vinylimidazole (VIm) were investigated and the reactivity ratios for each copolymerization system were determined. Thanks to these values a series of statistical copolymers with predictable composition and low deviation over the chain distribution could then be synthesized. Finally, the acidic hydrolysis of the acetamide functions towards the corresponding amine was performed and optimized. Copolymers containing various pendant amino groups and with low dispersity in the chain composition could be obtained, which opens new perspectives for the above mentioned applications. [less ▲]

Detailed reference viewed: 74 (27 ULiège)
See detailNon-viral vectors for gene delivery: cationic polymers
Dréan, Mathilde; Debuigne, Antoine ULiege; Rieger, Jutta ULiege et al

Poster (2015, December 17)

Detailed reference viewed: 14 (6 ULiège)
See detailSyntheses of polyvinylamine based copolymers
Dréan, Mathilde; Debuigne, Antoine ULiege; Guégan, Philippe et al

Conference (2015, December)

Detailed reference viewed: 25 (4 ULiège)
See detailNew polyvinylamine-based (co)polymers for nucleic acid delivery
Dréan, Mathilde; Debuigne, Antoine ULiege; Guégan, Philippe et al

Conference (2015, March)

Detailed reference viewed: 21 (2 ULiège)
See detailNew polyvinylamine-based (co)polymers for nucleic acid delivery
Dréan, Mathilde; Debuigne, Antoine ULiege; Guégan, Philippe et al

Conference (2014, March)

Detailed reference viewed: 10 (2 ULiège)