Synthesis and Self-Assembly of Xylan-Based Amphiphiles: From Bio-Based Vesicles to Antifungal Properties.

This work aims at designing functional biomaterials through selective chemical modification of xylan from beechwood. Acidic hydrolysis of xylan led to well-defined oligomers with an average of six xylose units per chain and with an aldehyde group at the reductive end. Reductive amination was performed on this aldehyde end group to introduce an azide reactive group. "Click chemistry" was then applied to couple these hydrophilic xylans moieties with different hydrophobic fatty acid methyl esters that were previously functionalized with complementary alkyne functions. The resulting amphiphilic bio-based conjugates were then self-assembled using three different methods, namely, direct solubilization, thin-film rehydration/extrusion, and microfluidics. Well-defined micelles and vesicles were obtained, and their high loading capacity with propiconazole as an antifungal active molecule was shown. The resulting vesicles loaded with propiconazole in a microfluidic process proved to significantly improve the antifungal activity of propiconazole, demonstrating the high potential of such xylan-based amphiphiles.

Disulfide-Functionalized Diblock Copolymer Worm Gels.

Two strategies for introducing disulfide groups at the outer surface of RAFT-synthesized poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) (PGMA-PHPMA, or Gx-Hy for brevity) diblock copolymer worms are investigated. The first approach involved statistical copolymerization of GMA with a small amount of disulfide dimethacrylate (DSDMA, or D) comonomer to afford a G54-D0.50 macromolecular chain transfer agent (macro-CTA); this synthesis was conducted in relatively dilute solution in order to ensure mainly intramolecular cyclization and hence the formation of linear chains. Alternatively, a new disulfide-based bifunctional RAFT agent (DSDB) was used to prepare a G45-S-S-G45 (or (G45-S)2) macro-CTA. A binary mixture of a non-functionalized G55 macro-CTA was utilized with each of these two disulfide-based macro-CTAs in turn for the RAFT aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA). By targeting a PHPMA DP of 130 and systematically varying the molar ratio of the two macro-CTAs, a series of disulfide-functionalized diblock copolymer worm gels were obtained. For both formulations, oscillatory rheology studies confirmed that higher disulfide contents led to stronger gels, presumably as a result of inter-worm covalent bond formation via disulfide/thiol exchange. Using the DSDB-based macro-CTA led to the strongest worm gels, and this formulation also proved to be more effective in suppressing the thermosensitive behavior that is observed for the nondisulfide-functionalized control worm gel. However, macroscopic precipitation occurred when the proportion of DSDB-based macro-CTA was increased to 50 mol %, whereas the DSDMA-based macro-CTA could be utilized at up to 80 mol %. Finally, the worm gel modulus could be reduced to that of a nondisulfide-containing worm gel by reductive cleavage of the inter-worm disulfide bonds using excess tris(2-carboxyethyl)phosphine (TCEP) to yield thiol groups. These new biomimetic worm gels are expected to exhibit enhanced muco-adhesion.

An arm-first approach to cleavable mikto-arm star polymers by RAFT polymerization.

Redox-cleavable mikto-arm star polymers are prepared by an "arm-first" approach involving copolymerization of a dimethacrylate mediated by a mixture of macroRAFT agents. Thus, RAFT copolymerization of the monomers BMA, DMAEMA, and OEGMA, with the disulfide dimethacrylate cross-linker (DSDMA), bis(2-methacryloyl)oxyethyl disulfide, mediated by a 1:1:1 mixture of three macroRAFT agents with markedly different properties [hydrophilic, poly[oligo(ethylene glycol) methacrylate]-P(OEGMA)8-9 ; cationizable, poly[2-(dimethylamino)ethyl methacrylate]-P(DMAEMA); hydrophobic, poly(n-butyl methacrylate)-P(BMA)] provides low dispersity mikto-arm star polymers. Good control (D < 1.3) is observed for the target P(DMAEMA)/P(OEGMA)/P(BMA) (3:3:1) mikto-arm star, a double hydrophilic P(DMAEMA)/P(OEGMA) (3:3) mikto-arm star and a hydrophobic P(BMA) homo-arm star. However, D for the target mikto-arm stars increases with an increase in either the ratio [DSDMA]:[total macroRAFT] or the fraction of hydrophobic P(BMA) macroRAFT agent. The quaternized mikto-arm star in dilute aqueous solution shows a monomodal particle size distribution and an average size of ≈145 nm.

Synthesis, characterization and stability of crosslinked chitosan-maltodextrin pH-sensitive nanogels.

Polysaccharide-based nanogels offer a wide range of chemical compositions and are of great interest due to their biodegradability, biocompatibility, non-toxicity, and their ability to display pH, temperature, or enzymatic response. In this work, we synthesized monodisperse and tunable pH-sensitive nanogels by crosslinking, through reductive amination, chitosan and partially oxidized maltodextrins, by keeping the concentration of chitosan around the overlap concentration, i.e. in the dilute and semi-dilute regime. The chitosan/maltodextrin nanogels presented sizes ranging from 63 ±â€¯9 to 279 ±â€¯16 nm, showed quasi-spherical and cauliflower-like morphology, reached a ζ-potential of +36 ±â€¯2 mV and maintained a colloidal stability for up to 7 weeks. It was found that the size and surface charge of nanogels depended both on the oxidation degree of maltodextrins and chitosan concentration, as well as on its degree of acetylation and protonation, the latter tuned by pH. The pH-responsiveness of the nanogels was evidenced by an increased size, owed to swelling, and ζ-potential when pH was lowered. Finally, maltodextrin-chitosan biocompatible nanogels were assessed by cell viability assay performed using the HEK293T cell line.

Chitosan-DNA polyelectrolyte complex: Influence of chitosan characteristics and mechanism of complex formation.

Polyelectrolyte complexes formed between DNA and chitosan present different and interesting physicochemical properties combined with high biocompatibility; they are very useful for biomedical applications. DNA in its double helical structure is a semi-rigid polyelectrolyte chain. Chitosan, an abundant polysaccharide in nature, is considered as one of the most attractive vectors due to its biocompatibility and biodegradability. Here we study chitosan/DNA polyelectrolyte complex formation mechanism and the key factors of their stability. Compaction process of DNA with chitosan was monitored in terms of the ζ-potential and hydrodynamic radius variation as a function of charge ratios between chitosan and DNA. The influence of chitosan degree of acetylation (DA) and its molecular weight on the stoichiometry of chitosan/DNA complexes characteristics was also studied. It is shown that the isoelectric point of chitosan/DNA complexes, as well as their stability, is directly related to the degree of protonation of chitosan (depending on pH), to the DA and to the external salt concentration. It is demonstrated that DNA compaction process corresponds to an all or nothing like-process. Finally, since an important factor in cell travelling is the buffering effect of the vector used, we demonstrated the essential role of free chitosan on the proton-sponge effect.

Swelling kinetics for a pH-induced latex-to-microgel transition.

The kinetics of swelling of a series of six near-monodisperse, lightly cross-linked poly(2-vinylpyridine) latexes with mean diameters ranging from 380 to 1010 nm has been investigated by the pH jump method using a commercial stopped-flow instrument. These pH-responsive particles become substantially protonated at around pH 4.1, which leads to a rapid latex-to-microgel transition within a time scale of tens of milliseconds. The characteristic swelling time correlates linearly with the mean particle diameter, as predicted by the Tanaka equation. However, faster swelling is observed in the presence of added salt. This is contrary to the theory developed by Tanaka, which assumes that the relaxation of the polymer chains is the rate-limiting step. An alternative viewpoint, in which infusion of solvent determines the characteristic swelling time, satisfactorily explains the experimental observations and collapses most of the data, except for the largest microgels. This discrepancy is suggested to be due to the inaccurate sizing of these micrometer-sized swollen microgels by dynamic light scattering.