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International audience; Poly(d,l-lactide-co-glycolide) (PLGA) copolyesters are commonly used in biomedical applications. Researches were carried out on nontoxic or low-toxic catalysts that are enough efficient to provide short polymerization times, adequate microstructure chains and similar properties than the commercial PLGA materials. In this study, PLGA were synthesized by ring-opening copolymerization (ROP) using three different catalysts. Stannous octoate is the first catalyst we used, as it is very efficient, even its toxicity is still on debate. Two others low-toxic catalysts [zinc lactate and bismuth subsalicylate (BiSS)] were also evaluated. The comparison of these ROP was realized in terms of kinetics and control of the polymerization. Then, the influence of the catalyst on the PLGA microstructure chains is reported. Finally, abiotic hydrolytic degradation rate is studied. Results described in this article show that BiSS is one very attractive catalyst to produce low toxic PLGA for biomedical applications.

The controlled synthesis of biodegradable copolymers of dextran grafted with aliphatic polyesters first requires the preparation of polysaccharide derivatives soluble in organic solvents. Silylation of dextran can thus lead to such organosoluble derivatives and allows the polymerization of cyclic esters initiated from the nonsilylated OH functions. Silylation of dextran was studied in DMSO by different reactants such as 1,1,1,3,3,3-hexamethyldisilazane (HMDS) in the presence of various catalysts and N,O-bis(trimethylsilyl)acetamide (BSA). According to the silylating agent and the used experimental conditions, it was possible to obtain highly or totally silylated dextrans. In parallel, an investigation of the chemical stability of the dextran chain during silylation was performed. Thus, it was found that, when used at 50 degrees C, HMDS with or without catalysts gives a relatively high silylation yield and does not alter the dextran chain length, whereas at 80 degrees C, dextran degradation was observed. BSA is a very good silylating agent, which allows reaching 100% silylation even at 50 degrees C but provokes the degradation of the polysaccharide chains. The work was completed by a study of the reactivity order of the glucosidic OH functions toward silylation reaction. This order was found to be (OH(2) > OH(4) > OH(3)) as already reported for other reactions. 2D-NMR of highly silylated dextrans demonstrated that they are constituted of both quantitatively silylated glucose units and two types of disilylated ones.

National audience

National audience

International audience; A cholesterol-based liquid crystal monomer, diethylene glycol cholesteryl ether acrylate (DEGCholA), has been successfully polymerized by atom transfer radical polymerization (ATRP) for the first time. Appropriate experimental conditions to control the polymerization of DEGCholA have been investigated using a model initiator (ethyl 2-bromoisobutyrate) in tetrahydrofuran (THF) or toluene at 60 degrees C. Well-controlled ATRP of DEGCholA was obtained using N,N,N',N',N `'-pentamethyldiethylenetriamine as ligand in THF at 60 degrees C. These conditions were then applied to initiate the ATRP of DEGCholA from multifunctional macroinitiators based on dextran. Using a protection/deprotection synthetic scheme, novel graft glycopolymers (Dex-g-PDEGCholA) have been synthesized. The mesomorphic properties of DEGCholA, PDEGCholA, and Dex-g-PDEGCholA have been studied by thermal polarizing optical microscopy, differential scanning calorimetry, and X-ray scattering. PDEGCholA and Dex-g-PDEGCholA show an interdigitated smectic A phase (SmAd) between T-g (similar to 30 degrees C) and around 170 degrees C.

To easily perform atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA) in homogeneous medium from unprotected polysaccharidic macroinitiators, the ATRP of MMA carried out in dimethylsulfoxide has been firstly reinvestigated using Cu(I)Br as metal catalyst and ethyl 2-bromoisobutyrate as initiator. Two ligands, 2,2′-bipyridyne (Bpy) and N-(n-propyl)-2-pyridylmethanimine (n-Pr-PMI), have been compared, as well as the addition of Cu(II)Br2 (10 molar % relative to Cu(I)Br) or the adjustment of experimental temperature (from 30 to 60 °C). Appropriate conditions were founded for both ligands to achieve a controlled ATRP. Bpy giving far much faster polymerization compared to n-Pr-PMI, n-Pr-MI was preferred as ligand for accurate tuning of the conversion. Experimental procedure was then applied to unprotected macroinitiators based on dextran to obtain amphiphilic poly(methyl methacrylate) grafted dextran. While homopolymerization was controlled in these conditions, parameters have to be adjusted for the hydrophilic unprotected macroinitiators to prevent gel formation and control ATRP.

International audience

International audience

International audience; The whole controlled synthesis of novel amphiphilic polylactide (PLA)-grafted dextran copolymers was achieved. The control of the architecture of suchbiodegradable and potentially biocompatible copolymers has required a three-step synthesis based on the “grafting from” concept. The first step consisted of the partial silylation of the dextran hydroxyl groups. This protection step was followed by the ring-opening polymerization of D,L-lactide initiated from the remaining OH functions of the partially silylated polysaccharide. The third step involved the silylether group deprotection under very mild conditions. Based on previous studies, in which the control of the first step was achieved, this study is focused on the last two steps. Experimental conditions were investigated to ensure a controlled polymerization of D,L-lactide, in terms of grafting efficiency, graft length, and transesterification limitation. After polymerization, the final step was studied in order to avoid degradation of both polysaccharide backbone and polyester grafts. The chemical stability of dextran backbone was checked throughout each step of the synthesis. PLA-grafted dextrans and PLA-grafted (silylated dextrans) were proved to adopt a core-shell conformation invarious solvents. Furthermore, preliminary experiments on the potential use of these amphiphilic grafted copolymers as liquid/liquid interface stabilizers were performed

International audience; A large variety of amphiphilic polylactide-grafted dextrans has been synthesized with controlled architecture through a three-step procedure: partial protection of the dextran hydroxyl groups by silylation; ring-opening polymerization of D,L-lactide initiated from remaining hydroxyl groups on partially silylated dextran; and silyl ether deprotection under very mild conditions. Throughout the synthesis, detailed characterizations of each step led to the control of copolymer architecture in terms of graft number and lengths of graft and backbone. Depending on their proportion in polylactide, these copolymers were either water-soluble or soluble in organic solvents. The potential of these amphiphilic grafted copolymers as surfactants was estimated. Their organization at air/water or dichloromethane/water interfaces was investigated by interfacial tension measurements. Self-organization in water or toluene was evaluated using fluorescence spectroscopy. Depending on its solubility, each copolymer showed noticeable surfactant properties and was able to produce either hydrophobic or hydrated microdomains in water or toluene solutions, respectively

Synthesis of novel grafted amphiphilic copolymers polylactide-grafted dextran was achieved. Macromolecular control of such biodegradable and potentially biocompatible copolymers requires a three-step synthesis based on the "grafting from" concept : partial protection of the dextran hydroxyl groups by silylation ; followed by ring opening polymerization of D, L-lactide initiated from remaining hydroxyls of this partially silylated dextran backbone. The third step involves the silylethers deprotection under very mild conditions.Throughout the synthesis, detailed studies of each step have led to stability of dextran backbone and control of copolymer architecture in terms of graft number and graft length. Tension and fluorescence experiments have given information about the organisation properties of these copolymers. The potential of such copolymers for formulation of nanospheres has been also studied.; De nouveaux copolymères amphiphiliques en peigne de type dextrane-g-polylactide ont été obtenus. Pour contrôler les paramètres macromoléculaires de ces copolymères biodégradables et potentiellement biocompatibles, leur synthèse est effectuée par la méthode du "grafting from" en trois étapes: silylation partielle des fonctions hydroxyle du dextrane ; polymérisation par ouverture de cycle du D,L-lactide à partir des fonctions alcool résiduelles situées sur le dextrane protégé, puis clivage des groupements silyléthers dans des conditions douces. Des études détaillées de chaque étape ont permis d'assurer la stabilité de la chaîne de dextrane et le contrôle de l'architecture des copolymères (nombre et longueur des greffons). Les propriétés d'organisation de ces produits ont été évaluées à la fois par tensiométrie et spectroscopie de fluorescence. Ces propriétés nous ont permis d'envisager l'emploi de ces copolymères pour la préparation de nanosphères.

Synthesis of novel grafted amphiphilic copolymers polylactide-grafted dextran was achieved. Macromolecular control of such biodegradable and potentially biocompatible copolymers requires a three-step synthesis based on the "grafting from" concept : partial protection of the dextran hydroxyl groups by silylation ; followed by ring opening polymerization of D, L-lactide initiated from remaining hydroxyls of this partially silylated dextran backbone. The third step involves the silylethers deprotection under very mild conditions.Throughout the synthesis, detailed studies of each step have led to stability of dextran backbone and control of copolymer architecture in terms of graft number and graft length. Tension and fluorescence experiments have given information about the organisation properties of these copolymers. The potential of such copolymers for formulation of nanospheres has been also studied., De nouveaux copolymères amphiphiliques en peigne de type dextrane-g-polylactide ont été obtenus. Pour contrôler les paramètres macromoléculaires de ces copolymères biodégradables et potentiellement biocompatibles, leur synthèse est effectuée par la méthode du "grafting from" en trois étapes: silylation partielle des fonctions hydroxyle du dextrane ; polymérisation par ouverture de cycle du D,L-lactide à partir des fonctions alcool résiduelles situées sur le dextrane protégé, puis clivage des groupements silyléthers dans des conditions douces. Des études détaillées de chaque étape ont permis d'assurer la stabilité de la chaîne de dextrane et le contrôle de l'architecture des copolymères (nombre et longueur des greffons). Les propriétés d'organisation de ces produits ont été évaluées à la fois par tensiométrie et spectroscopie de fluorescence. Ces propriétés nous ont permis d'envisager l'emploi de ces copolymères pour la préparation de nanosphères.

International audience; The strong associative behaviour between cholesterol-modified dextran (CMD) and short and long polyoxyethylene cholesteryl ether (ChEO10) micelles were investigated using rheology and small-angle neutron scattering (SANS). In solutions of short rod-like micelles (ChEO10 alone), the addition of 5.0 wt% CMD induced a remarkable transition from a Newtonian system to a highly solid-like viscoelastic network, with an increase in zero-shear viscosity of over 5 orders of magnitude. The frequency sweeps at ChEO10 concentrations above 2.5 wt% were fitted to a Maxwell model with 3 elements and, quite remarkably, fell onto a single master curve, while no network was formed at 2.5 wt% micelles. Viscoelastic solutions of wormlike micelles (WLMs) were obtained by adding the co-surfactant triethylene glycol monododecyl ether (C12EO3) to ChEO10 solutions at a constant ChEO10/C12EO3 ratio of 5/1. The introduction of CMD into the WLM solutions induced a transition to a more liquid-like behaviour (G″/G′ increased), however both moduli increased by one order of magnitude. At the lowest ChEO10 concentration (2.5%), the solid-like behaviour was lost. Overall, a comparable rheological response was obtained for the WLM and the short rods with CMD, however the WLM/CMD behaviour suggested a wider spectrum of relaxation processes, longer relaxation times and higher plateau moduli. SANS data from the polymer/micelles mixtures displayed a strong structural peak and were remarkably identical for both ChEO10/CMD and ChEO10/C12EO3/CMD systems, suggesting a very similar type of network structure, independently of the initial size of the micelles. Overall, all the results taken together show a very high affinity between the polymer and the micelles and suggest a breakup of the WLM induced by CMD. The resulting network is constituted by polymeric chains connected by micellar aggregates through hydrophobic interactions between the micellar cholesterol cores and the pendent cholesterol moieties of the polymer