Jérôme Babin

A new two-photon-sensitive block copolymer nanocarrier.

Easily disrupted: Micelles of a new amphiphilic block copolymer that bear coumarin groups are sensitive to near infrared light by two-photon absorption of the chromophore. Disruption of the micelles under irradiation at 794 nm results in release of both photocleaved coumarin and encapsulated nile red from the hydrophobic core of micelle into aqueous solution, which results in opposing changes in fluorescence emission intensity.

MRI observation of the light-induced release of a contrast agent from photo-controllable polymer micelles.

The encapsulation of molecules into nanocarriers is studied for its potential in delivering a high dose of anticancer drugs to a tumor, while minimizing side effects. Most systems either release their content in a non-specific manner or under specific environmental conditions such as temperature or pH. We have synthesized a novel class of photo-controllable polymer micelles that can stably encapsulate a hydrophilic compound and subsequently release it upon absorption of UV light. Here, we describe an in vitro magnetic resonance imaging assay that can evaluate the state of incorporation of a small Gd-based contrast agent. Our results indicate that the contrast agent alone can diffuse through a filter, but that the same agent incorporated into micelles cannot. After exposure to UV light, the micelles released the contrast agent, which could then diffuse through the filter.

Polysaccharide-covered nanoparticles with improved shell stability using click-chemistry strategies

Dextran-covered PLA nanoparticles have been formulated by two strategies. On one hand, dextran-g-PLA copolymers have been synthesized by click-chemistry between azide-multifunctionalized dextran (DexN3) and alkyne end-functionalized PLA chains (α-alkyne PLA); then nanoprecipitated without any additional surfactants. On the other hand, DexN3 exhibiting surfactant properties have been emulsified with unfunctionalized or α-alkyne PLA, which are dissolved in organic phase with or without CuBr. Depending on the o/w emulsion/evaporation process experimental conditions, dextran-g-PLA copolymers have been produced in situ, by click chemistry at the liquid/liquid interface during the emulsification step. Whatever the process, biodegradable core/shell polymeric nanoparticles have been obtained, then characterized. Colloidal stability of these nanoparticles in the presence of NaCl or SDS has been studied. While the physically adsorbed polysaccharide based shell has been displaced by SDS, the covalently-linked polysaccharide based shell ensures a permanent stability, even in the presence of SDS.

Amphiphilic photosensitive dextran-g-poly(o-nitrobenzyl acrylate) glycopolymers.

Among all photosensitive monomers reported in the literature, o-nitrobenzyl acrylate (NBA) was selected in this present study. Two strategies were compared to produce azido-terminated poly(o-nitrobenzyl acrylate) (PNBA) using controlled Single Electron Transfer-Living Radical Polymerization (SET-LRP). In a parallel way, dextran (Dex) was modified by the introduction of several alkynyl-terminated hydrophobic chains. Finally, an Huisgen-type Copper (I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) click-chemistry was carried out to produce amphiphilic Dex-g-PNBA glycopolymers with different number and length of PNBA grafts. 2D DOSY (1)H NMR was used to prove the formation of such glycopolymers. Preliminary study on Dex-g-PNBA self-assembly was done by measuring the critical water content (CWC) above which Dex-g-PNBA started to auto-organize themselves to produce nano-objects. Finally, under UV irradiation, PNBA grafts turn into poly(acrylic acid) ones giving light-sensitive properties to such amphiphilic Dex-g-PNBA. Such properties were evaluated and compared with those of PNBA.

Grafting of cellulose acetate with ionic liquids for biofuel purification by a membrane process: Influence of the cation

A new strategy was developed for grafting ionic liquids (ILs) onto cellulose acetate in order to avoid IL extraction and improve its performance for ethyl tert-butyl ether (ETBE) biofuel purification by the pervaporation membrane process. This work extended the scope of IL-containing membranes to the challenging separation of organic liquid mixtures, in which these ILs were soluble. The ILs contained the same bromide anion and different cations with increasing polar feature. The membrane properties were strongly improved by IL grafting. Their analysis in terms of structure-property relationships revealed the influence of the IL content, chemical structure and chemical physical parameters α, β, π* in the Kamlet-Taft polarity scale. The ammonium IL led to the best normalized flux of 0.182kg/m(2)h for a reference thickness of 5μm, a permeate ethanol content of 100% and an outstanding infinite separation factor for the azeotropic mixture EtOH/ETBE at 50°C.

Multiblock Copolymer Grafting for Butanol Biofuel Recovery by a Sustainable Membrane Process.

Biobutanol is an attractive renewable biofuel mainly obtained by the acetone-butanol-ethanol (ABE) fermentation process. Nevertheless, the alcohol concentration has to be limited to a maximum of 2 wt % in ABE fermentation broths to avoid butanol toxicity to the microorganisms. The pervaporation (PV) membrane process is a key sustainable technology for butanol recovery in these challenging conditions. In this work, the grafting of azido-polydimethylsiloxane (PDMS-N3) onto a PDMS-based multiblock copolymer containing alkyne side groups led to a series of original membrane materials with increasing PDMS contents from 50 to 71 wt %. Their membrane properties were assessed for butanol recovery by pervaporation from a model aqueous solution containing 2 wt % of n-butanol at 50 °C. The membrane flux J50μm for a reference thickness of 50 μm strongly increased from 84 to 192 g/h m(2) with increasing PDMS content for free-standing dense membranes with thicknesses in the range of 38-95 μm. At the same time, the intrinsic butanol permeability increased from 1.47 to 4.68 kg μm/h m(2) kPa and the permeate butanol content was also strongly improved from 38 to 53 wt %, corresponding to high and very high membrane separation factors of 30 and 55, respectively. Therefore, the new grafted copolymer materials strongly overcame the common permeability/selectivity trade-off for butanol recovery by a sustainable membrane process.

First multi-reactive dextran-based inisurf for atom transfer radical polymerization in miniemulsion

A multi-reactive polysaccharide-based inisurf (acting both as initiator and stabilizer) has been designed for the first time from dextran with the aim of preparing dextran-covered nanoparticles with covalent linkage between core and coverage. This inisurf was used for polymerizing butyl acrylate in miniemulsion by AGET-ATRP. Both hydrophobic phenoxy groups and initiator groups (bromoisobutyryl ester) were introduced within hydrophilic dextran chain, conferring it amphiphilic and macroinitiator characters. Amphiphilic properties of dextran inisurfs have been evidenced as well as their ability to stabilize the direct miniemulsion of n-butyl acrylate. After optimization of polymerization conditions with model studies, assays were successfully realized with dextran-based inisurfs. Because of their amphiphilic character, inisurfs migrated at oil/water interface and initiated polymerization from bromoisobutyryl ester groups. Therefore graft copolymers were produced at oil/water interface, due to the multifunctional character of these inisurfs and constituted the particle inner core with covalent links to the dextran coverage.

Stability of a biodegradable microcarrier surface: physically adsorbed versus chemically linked shells

Mesenchymal stem cells (MSCs) have gained increasing interest for tissue engineering and cellular therapy. MSC expansion on microcarriers (MCs) in stirred bioreactors has emerged as an attractive method for their scaled up production. Some MCs have been developed based on polyesters as a hydrophobic biodegradable core. However, most of these MCs are formulated by an emulsion/organic solvent evaporation (E/E) process using poly(vinyl alcohol) as a shell steric stabilizer, which is biocompatible but not degradable in vivo. Moreover, in most of these MCs, the polymer shell is only physically adsorbed at the particle surface. To the best of our knowledge, no study deals with the stability of such a shell when the MCs are in contact with competitive surfactants or with proteins contained in the culture medium. In this study, fully in vivo bioresorbable dextran-covered polylactide-based MCs were formulated using an E/E process, which allowed to control their surface chemistry. Different dextran derivatives with alkyne or ammonium groups were firstly synthesised. Then, on the one hand, some MCs (non-clicked MCs) were formulated with a physically adsorbed polysaccharide shell onto the core. On the other hand, the polysaccharide shell was linked to the core via in situ CuAAC click-chemistry carried out during the E/E process (clicked MCs). The stability of such coverage was first studied in the presence of competitive surfactants (sodium dodecyl sulfate-SDS, or proteins contained in the culture medium) using nanoparticles (NPs) exhibiting the same chemical composition (core/shell) as MCs. The results revealed the total desorption of the dextran shell for non-clicked NPs after treatment with SDS or the culture medium, while this shell desorption was greatly decreased for clicked NPs. A qualitative study of this shell stability was finally carried out on MCs formulated using a new fluorescent dextran-based surfactant. The results were in agreement with those observed for NPs, and showed that non-clicked MCs are characterized by poor shell stability in contact with a competitive surfactant, which could be quite an issue during MSC expansion. In contrast, clicked MCs possess better shell stability, which allow a better control of the MC surface chemistry, especially during cell culture.

Grafting cellulose acetate with ionic liquids for biofuel purification membranes : Influence of the anion

Membranes made from cellulose acetate grafted with imidazolium or ammonium ionic liquids (ILs) containing different anions were considered for ethyl tert-butyl ether biofuel purification by pervaporation. The new cellulosic materials were obtained after bromide (Br-) exchange by different anions (Tf2N-, BF4-, AcO-). IL structure-membrane property relationships revealed that the membrane properties were strongly improved by varying the anion structure, molecular size and hydrogen bonding acceptor ability β in the Kamlet-Taft polarity scale. The grafted ammonium IL with AcO- anion combined the highest parameter β with big cation/anion sizes and finally led to the best membrane properties with a normalized pervaporation flux of 0.41 kg/h m2 (almost 20 times that of virgin cellulose acetate) for a reference thickness of 5 μm and a permeate ethanol content of 100%. Such properties thus corresponded to an outstanding separation factor at 50 °C.

Mechanical properties evolution of a PLGA-PLCL composite scaffold for ligament tissue engineering under static and cyclic traction-torsion in vitro culture conditions

This study aims to investigate the in vitro degradation of a poly(L-lactic-co-glycolic acid)-poly(L-lactic-co-ϵ-caprolactone) (PLGA-PLCL) composite scaffold’s mechanical properties under static culture condition and 2 h period per day of traction-torsion cyclic culture conditions of simultaneous 10% uniaxial strain and 90° of torsion cycles at 0.33 Hz. Scaffolds were cultured in static conditions, during 28 days, with or without cell seeded or under dynamic conditions during 14 days in a bioreactor. Scaffolds’ biocompatibility and proliferation were investigated with Alamar Blue tests and cell nuclei staining. Scaffolds’ mechanical properties were tested during degradation by uniaxial traction test. The PLGA-PLCL composite scaffold showed a good cytocompatibility and a high degree of colonization in static conditions. Mechanical tests showed a competition between two process of degradation which have been associated to hydrolytic and enzymatic degradation for the reinforce yarn in poly(L-lactic-co-glycolic acid) (PLGA). The enzymatic degradation led to a decrease effect on mechanical properties of cell-seeded scaffolds during the 21st days, but the hydrolytic degradation was preponderant at day 28. In conclusion, the structure of this scaffold is adapted to culture in terms of biocompatibility and cell orientation (microfiber) but must be improved by delaying the degradation of it reinforce structure in PLGA.