Laurent Bouteiller

Aqueous Polysaccharide Associations Mediated by β-Cyclodextrin Polymers

Macromolecular assemblies were elaborated by mixing in water hydrophobically modified dextrans (MDC(n)) and beta-cyclodextrin polymers (pbetaCD) interacting by inclusion complexation between the hydrophobic moieties of MDCn and the beta-cyclodextrin cavities of pbetaCD. Dextrans have been modified by grafting alkyl groups (C(n)) of varying chain lengths (n = 8-16) and grafting ratio (3-6 mol%). Different pbetaCD polymers were synthesized by polycondensation of beta-cyclodextrin and epichlorohydrin. The polymer-polymer interactions have been studied by fluorimetry, isothermal titration microcalorimetry, phase diagrams, and viscosimetry. The viscoelastic properties of the temporary networks (in the semidilute range) have been studied by rheology. The interaction mechanisms between the MDCn and pbetaCD can be understood taking into account the strength of the interaction between the alkyl group and the beta-cyclodextrin cavity (mainly controlled by the alkyl chain length), the density of junctions between the chains (depending on the alkyl grafting density and the pbetaCD molecular weight), and additional cooperative effect (arising for high alkyl grafting density).

Synthesis and ITC characterization of novel nanoparticles constituted by poly(gamma-benzyl L-glutamate)-beta-cyclodextrin.

Imparting desired technological characteristics to polymeric nanoparticles requires the development of original polymers. In the present work, the synthesis and characterization of a novel PBLG‐derivative, the poly(γ‐benzyl L‐glutamate)‐β‐cyclodextrin (PBLG‐β‐CD‐50), have been carried out. Nanoparticles from either PBLG‐β‐CD‐50 polymer or from mixtures with PBLG have been prepared using a modified nanoprecipitation method. Spherically shaped nanoparticles with diameter in the range of 50–70u2009nm were obtained, as determined by dynamic laser light scattering and transmission electron microscopy. The presence of a surfactant in the suspension medium had almost no influence on these parameters and was not necessary to the shelf‐stability of the suspension. Further, isothermal titration microcalorimetry (ITC) experiments have been used to show unambiguously that about 20% of the cyclodextrins remain functional within the particles. Consequently, this system may be of interest when association of large amounts of hydrophobic drugs to nanoparticles is required. Copyright

PEGylated degradable composite nanoparticles based on mixtures of PEG-b-poly(γ-benzyl L-glutamate) and poly(γ-benzyl L-glutamate).

In the present work, the possibility to obtain PEGylated nanoparticles from two PBLG derivatives, PEG-b-poly(γ-benzyl L-glutamate), PBLG-PEG-60, and poly(γ-benzyl L-glutamate), PBLG-Bnz-50, by nanoprecipitation has been investigated. Particles were prepared not only from one polymer (PBLG-PEG-60 or PBLG-Bnz-50), but also from mixtures of two PBLG derivatives, PBLG-PEG-60 and PBLG-Bnz-50, in different ratios (90/10, 77/23, and 40/60 wt %). Because of the presence of PEG chains, hydrophilic particles were obtained, which was confirmed by ζ potential measurements (ζ from -13 mV and -21 mV) and by isothermal titration microcalorimetry (ITC). This last technique has shown no heat exchange when BSA was added to PEGylated nanoparticles. Further, complement activation has been evaluated by crossed immuno-electrophoresis demonstrating that the introduction of 77 wt % of PEGylated PBLG chains in the particles was enough to ensure a low complement activation activity. This effect was strongly correlated to the ζ potential of the particles, which decreased with an increase of PEG chains content. Interestingly, such properties are of interest for the preparation of degradable stealth nanocarriers. Moreover, it is suggested that the introduction of a reasonable amount (up to 20 wt %) of a second copolymer in the particle composition can be possible without modifying their stealth character. Moreover, the presence of this second copolymer would help to introduce a second functionality to the particles.

Tuning reversible supramolecular polymer properties through co-monomer addition

Unlike most low molar mass organogelators, which form strong gels due to the entanglement of strong molecular aggregates such as crystalline fibres, a few reversible supramolecular polymers form viscoelastic solutions due to the formation of both rigid and dynamic filaments. By using three different bisureas which self-assemble according to the same hydrogen-bonding pattern and form such rigid reversible supramolecular polymers, we have shown that it is possible to finely tune the properties of the resulting solutions. The critical temperature below which viscoelastic solutions are obtained and the viscosity of the dilute solutions can be adjusted by changing the co-monomer content. This clearly facilitates gel formulation, which is an important step as far as applications are concerned. By using three different bis-ureas which self-assemble according to the same hydrogen bonding pattern and form rigid reversible supramolecular polymers, we show that it is possible to finely tune the properties of the resulting viscoelastic solutions.

Stable low molecular weight glasses based on mixtures of bisphenol-A and bispyridines

Low molecular weight organic glasses were made by melt mixing two crystalline solids: bisphenol A and various bispyridines. Stable glasses were obtained because of intermolecular hydrogen bond formation between phenol and pyridine groups. The composition dependence of the Tg of the mixtures shows a very strong and positive deviation from the behavior of ideal copolymers or ideal polymer blends. Moreover, the strong influence of the structure of the low molecular weight compounds on the Tg of the mixture can be adequately described by empirical relationships, which are known in the field of polymers.