Emmanuelle Marie

Biodegradable nanoparticles made from polylactide-grafted dextran copolymers

Polysaccharide-covered polyester nanoparticles were prepared using the emulsion/solvent evaporation process. The core of the nanoparticles was made either of PLA or of a blend of polylactide and polylactide-grafted dextran copolymer in various proportions. The surface of the nanoparticles was covered by dextran chains via the use of water-soluble polylactide-grafted dextrans as polymeric stabilizers during the emulsification step. The characteristics of the nanoparticles (size, surface coverage, thickness of superficial layer, colloidal stability) were correlated to the structural parameters (length and number of polylactide grafts) of the copolymers as well as to their surface active properties. The complete biodegradability of the nanoparticles was evaluated by considering the rate of hydrolysis of polylactide grafts in phosphate buffer and the rate of enzymatic degradation of dextran backbone by dextranase.

Poly(n-butyl cyanoacrylate) nanoparticles via miniemulsion polymerization. 2. PEG-based surfactants

This study aimed at synthesizing PEG-coated poly(n-butyl cyanoacrylate) nanoparticles by miniemulsion polymerization. Despite the high reactivity of butyl cyanoacrylate, nanoparticles were successfully obtained by miniemulsion polymerization of butyl cyanoacrylate-in-water emulsions stabilized by three PEG-based surfactants: Brij78, Brij700, and Tween80. Their physico-chemical properties were thoroughly investigated as a function of surfactant structure and concentration and discussed on the basis of results obtained from interfacial tension measurements (dodecane-water). Results clearly showed the influence of the length of the PEG part of the surfactant on the final properties of the particles.

PEO‐Covered Nanoparticles by Emulsion Inversion Point (EIP) Method

This study reports the first PEO-coated polymer nanoparticles synthesis by miniemulsion polymerization of nano-emulsions prepared by the low-energy emulsification method called EIP. The surfactant used was Brij 98, a PEO based non ionic commercial surfactant. The partial phase diagram of the system water/Brij 98/styrene was first determined. The Emulsion Inversion Point technique was then used on the water/Brij 98/styrene system to the formation of styrene-in-water nano-emulsions. After miniemulsion polymerization, particle sizes as low as 36 nm were obtained. To the best of our knowledge, this method had not been used for polymerizable system up to now.

Macromolecular surfactants for miniemulsion polymerization

The use of polymeric surfactants as stabilizers in miniemulsion polymerization was reviewed. The structural characteristics of reported polymeric surfactants were detailed and compared. The concept of multi-functional polymeric surfactants was evidenced. The specificities brought by polymeric surfactants in the process of miniemulsion polymerization in comparison to molecular surfactants were analysed for the stability of the initial monomer emulsion, polymerization kinetics and characteristics of the obtained latexes. The contribution of polymeric surfactants to the control of the characteristics of the obtained nanoparticles was detailed with regard to the nature of the core material and to the surface coverage. Polymeric surfactants can be seen as powerful tools for the design of original nanoparticles. On the basis of the available data, possible research topics are suggested.

Lipase-catalyzed synthesis of hydrophobically modified dextrans: Activity and regioselectivity of lipase from Candida rugosa

Vinyl decanoate-modified dextran macromolecules (DexT40-VD) were synthesized in dimethyl sulfoxide at 50°C using lipase AY from Candida rugosa for catalyzing transesterification between polysaccharide and vinyl fatty esters. The extent of dextran modification (quantified by the molar ratio of attached alkyl tails to sugar repeat units) with native-, pH-adjusted-, 18-crown-6 ether pretreated pH-adjusted-, and stepwise addition of pretreated lipase AY yielded <3%, 49%, 64% and 96% modified dextran respectively. Lipase AY accelerated the transesterification of DexT40 from 2- to 63-fold higher than the non-catalyzed system. This procedure was extended to other acyl donors showing that modification pattern exhibited regioselectivity depending on acyl donor structure. Regioselectivity equaled between 2- and 3-OH with saturated fatty acyl donors. The 2-OH was favored for unsaturated fatty acyl donors, while sterically hindered acyl donors oriented modification toward 3-OH position. DexT40-VD at 96% modification was a water-insoluble polymer forming 150nm diameter nanoparticles in water which can be used as drug carrier systems.

Miniemulsion polymerizations of n-butyl cyanoacrylate via two routes: towards a control of particle degradation.

This study aimed at determining the influence of the mechanism of polymerization on the molar mass and degradation of poly(n-butyl cyanoacrylate) (PBCA) nanoparticles obtained by miniemulsion polymerization. Therefore, nanoparticles of poly(n-butyl cyanoacrylate) were synthesized via radical and/or anionic miniemulsion polymerization stabilized by Brij®78, a POE based surfactant. Polymerization conditions had little influence on the final diameter while it severely affected the final molar masses of PBCA. An increase of the temperature and of the pH of the continuous phase led to higher molar masses. A further increase was observed when a radical initiator was added in the monomer. The evolution of the molar mass of the synthesized poly(n-butyl cyanoacrylate) was followed as a function of time at pH 7.4 by Size Exclusion Chromatography. As expected, the degradation kinetics strongly depended on the polymerization mechanism (anionic or radical).

Synthesis of water-soluble and water-insoluble amphiphilic derivatives of dextran in organic medium

Hydrophobically modified dextrans were prepared by reacting native polysaccharide with 1,2-epoxydodecane in dimethylsulfoxide. Epoxide oligomerization was shown to occur as a secondary reaction when hydroxide ions were used as base catalysts. By adjusting the amount of epoxide in the feed, dextran derivatives with degrees of substitution (DS) between 0% and 164% were obtained. Polymers with DS above 100% were readily soluble in organic solvents like tetrahydrofuran, dioxane and water-saturated chloroform and dichloromethane. Their solution properties in organic solvent were characterized by capillary viscometry. Water-soluble derivatives were compared to other amphiphilic dextrans obtained using a heterogeneous modification in aqueous medium. The effect of modification conditions on substitution pattern was evidenced.

Toward one-pot lipase-catalyzed synthesis of poly(ɛ-caprolactone) particles in aqueous dispersion

The preparation of polyester particles using enzyme-catalyzed (lipase from Candida antarctica B, CALB) ring-opening polymerization of ε-caprolactone (ε-CL) in aqueous dispersion was demonstrated for the first time. Immobilization of CALB enabled a significant increase of the number-average degree of polymerization of ε-CL oligomers (up to 38) as compared to dissolved CALB (8 at the maximum). The nature and amount of lipase, as well as the nature of the support material were identified as key parameters controlling ring-opening polymerization of ε-CL in aqueous dispersion. In addition, the involvement of solubilized monomers in polymerization elementary reactions was demonstrated and the consequences on oligomers average length were detailed. An overall mechanism of lipase-catalyzed ε-CL polymerization in aqueous dispersion taking into account the colloidal nature of reaction medium was proposed on the basis of experimental results.

Temperature-Switchable Control of Ligand Display on Adlayers of Mixed Poly(lysine)- g -(PEO) and Poly(lysine)- g -(ligand-modified poly- N -isopropylacrylamide)

Adlayers of poly(lysine)-g-PEG comblike copolymer are extensively used to prepare cell-repellant and protein-repellent surfaces by a straightforward coulomb-driven adsorption that is compatible with diverse substrates (glass, Petri dish, etc.). To endow surfaces with functional properties, namely, controlled ligand-protein binding, comblike poly(lysine) derivatives were used to deposit temperature-responsive poly(NIPAM) macrografts mixed with PEG ones on glass surfaces. Simple surface immersion in mixed solutions of biotin-modified poly(lysine)-g-poly(N-isopropylacrylamide) and poly(lysine)-g-poly(ethylene oxide) yielded robust adlayers whose composition reflected the ratio between the two polymers in solution. We show by fluorescence imaging, and comparison with repellent 100% PEGylated patterns, that specific binding of model avidin/particle conjugates (diameters of ca. 10 or 200 nm) was controlled by temperature switch. The biotin ligand was displayed and accessible at low T, or hidden at T > LCST. Topography and mechanical mapping measurements by AFM confirmed the swelling/collapse status of PNIPAM macrografts in the adlayer at low/high T, respectively. Temperature-responsive comblike PLL derivative that can spontaneously cover anionic interfaces is a promising platform enabling good control on the deposition and accessibility of biofunctional groups on various solid surfaces.

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.