Poly(vinyl alcohol)s and Their Glycoderivatives as Efficient Shell-Builders of Nanocapsules by Nanoprecipitation.

Poly(vinyl alcohol)s (PVAs) are very popular dispersants for the construction of colloids and common shell-constituents of microcapsules but remain mostly unexplored as building blocks for the design of nanocapsules through nanoprecipitation or other processes. Herein, we first show that model commercial PVAs and oils can be concomitantly engaged in solvent-shifting procedures to give rise to oil-filled nanocapsules in one step. Next, we report the synthesis of precisely defined water-soluble glyco-PVAs by reversible addition-fragmentation chain transfer (RAFT) copolymerization of 6-O-vinyladipoyl-d-glucopyranose and vinyl chloroacetate and selective alcoholysis reactions. We finally demonstrate that these glycopolymers are excellent candidates for the straightforward conception of oil- and drug-filled, surface- and/or core-tagged, stealth, and degradable nanocapsules by nanoprecipitation.

Nanoassemblies of Chitosan-Based Polyelectrolyte Complexes as Nucleic Acid Delivery Systems.

Nucleic acid delivery requires vectorization for protection from nucleases, preventing clearance by the reticuloendothelial system, and targeting to allow cellular uptake. Nanovectors meeting the above specifications should be safe for the patient, simple to manufacture, and display long-term stability. Our nanovectors were obtained via the green process of polyelectrolyte complexation, carried out at 25 °C in water at a low shear rate using chitosan (a polycationic biocompatible polysaccharide of specific molar mass and acetylation degree) and dextran sulfate as a polyanionic biocompatible polysaccharide. These complexes formed nanoassemblies of primary nanoparticles (20-35 nm) and maintained their colloidal stability for over 1 year at 25 °C. They could be steam sterilized, and a model nucleic acid could be either encapsulated or surface adsorbed. A targeting agent was finally bound to their surface. This work serves as a proof of concept of the suitability of chitosan-based polyelectrolyte complexes as nanovectors by sequential multilayered adsorption of various biomacromolecules.

Wet-Spun Chitosan-Sodium Caseinate Fibers for Biomedicine: From Spinning Process to Physical Properties.

We designed and characterized chitosan-caseinate fibers processed through wet spinning for biomedical applications such as drug delivery from knitted medical devices. Sodium caseinate was either incorporated directly into the chitosan dope or allowed to diffuse into the chitosan hydrogel from a coagulation bath containing sodium caseinate and sodium hydroxide (NaOH). The latter route, where caseinate was incorporated in the neutralization bath, produced fibers with better mechanical properties for textile applications than those formed by the chitosan-caseinate mixed collodion route. The latter processing method consists of enriching a pre-formed chitosan hydrogel with caseinate, preserving the structure of the semicrystalline hydrogel without drastically affecting interactions involved in the chitosan self-assembly. Thus, dried fibers, after coagulation in a NaOH/sodium caseinate aqueous bath, exhibited preserved ultimate mechanical properties. The crystallinity ratio of chitosan was not significantly impacted by the presence of caseinate. However, when caseinate was incorporated into the chitosan dope, chitosan-caseinate fibers exhibited lower ultimate mechanical properties, possibly due to a lower entanglement density in the amorphous phase of the chitosan matrix. A standpoint is to optimize the chitosan-caseinate composition ratio and processing route to find a good compromise between the preservation of fiber mechanical properties and appropriate fiber composition for potential application in drug release.

Functional Hybrid Glyconanocapsules by a One-Pot Nanoprecipitation Process.

Herein, we report on one-pot fabrication of oil-filled nanocapsules wrapped with both RAFT-made glycopolymers and neutral polysaccharides (dextran and pullulan). We have made use of the nanoprecipitation technique, relying on coprecipitation of both oil and polymers in conditions thoroughly established from phase diagrams' interpretation. Mixed mono- or multilayered nanocapsules were obtained through simultaneous or sequential nanoprecipitations, respectively. Incorporation of synthetic glycopolymer chains allows for precisely tailoring the dimensions of the nanocapsules (size and membrane thickness of the polymeric shell), whereas the insertion of polysaccharides enables to tune the (bio)degradability of the nanocapsules. Shell-functionalized and/or core-loaded capsules could also be achieved in a similar one-pot process, by introducing a drug and/or biotin in the organic and aqueous phase, respectively.

In situ synthesis of Fe3O4 nanoparticles coated by chito-oligosaccharides: physico-chemical characterizations and cytotoxicity evaluation for biomedical applications.

Fe3O4 nanoparticles coated with chito-oligosaccharides (COS) were prepared in situ by a simple co-precipitation method through a mixing of iron ions (Fe3+ and Fe2+) and COS aqueous solutions followed by precipitation with ammonia. The impact of COS with different degree of polymerization (DP 10, 24 and 45) and degree of N-acetylation (DA) âˆ¼ 24% and 50% (exhibiting high solubility) on the synthesis and physical properties of the coated magnetic nanoparticles was evaluated. Several advantages were found when the magnetic nanoparticles were prepared in the presence of the studied COS, such as: preparation of functionalized magnetic nanoparticles with narrower size distributions and, consequently, higher saturation magnetization (an increase of up to 22%); and an expressive increasing in the concentration of COS-coated magnetic nanoparticles (up to twice) in the cell viability test in comparison with pure Fe3O4 nanoparticles. Furthermore, among the analyzed samples, the magnetic nanoparticles coated by COS with DA âˆ¼ 50% present a higher cytocompatibility. Our results allow envisioning various biomedical applications, valorizing the use of coated-magnetic nanoparticles for magnetic-field assisted drug delivery, enzyme or cell immobilization, or as a marker for specific cell tracking, among others.

Programmable Hierarchical Construction of Mixed/Multilayered Polysaccharide Nanocapsules through Simultaneous/Sequential Nanoprecipitation Steps.

We report here on a one-pot construction of oil-filled hierarchical capsular assemblies using the nanoprecipitation technique. Relying on multicomponent phase diagrams, we show that simultaneous and/or sequential nanoprecipitations involving polymer combinations can be precisely programmed to design a new class of mixed/multilayered multicomponent nanocapsules, with a precise control of the dimensions, shell thickness/composition, and spatial distribution of the building blocks. The simplicity and tunability of this approach are exemplified here with a library of neutral and ionic polysaccharides giving access to a range of functional multilayered nanocarriers of interest for biomedical applications.

Nanofluidics Approach to Separate between Static and Kinetic Nanoconfinement Effects on the Crystallization of Polymers.

Here we report a nanofluidics approach that allows one to discriminate, for the first time, between static and kinetic effects on the crystallization of polymers in 2-dimensional nanoconfinement. Nanofluidics cells designed to monitor in real time, via permittivity measurements, the flow process of polymers into cylindrical nanopores were employed to investigate the crystallization of poly(vinylidenefluoride-co-trifluoroethylene) (PVDF-TrFE) under static and under kinetic confinement conditions. A significant separation between static confinement effects and flow effects in confinement is reported. A characteristic time is deduced, to quantify the impact of flow on the crystallization process of polymers taking place under conditions of 2D geometrical nanoconfinement.

Simple but precise engineering of functional nanocapsules through nanoprecipitation.

A general, rapid, and undemanding method to generate at will functional oil-filled nanocapsules through nanoprecipitation is reported. On the basis of polymer and hexadecane/water/acetone phase diagrams, the composition can be set so that polymer chains preferentially stick at the interface of the oil droplets to create nanocapsules. The nanocapsules can be decorated with biorelevant molecules (biotin, fluorescent tags, metal nanoparticles) within the shell and loaded with hydrophobic molecules in a simple one-pot procedure.

Green nondegrading approach to alkyne-functionalized cellulose fibers and biohybrids thereof: synthesis and mapping of the derivatization.

Alkyne-functionalized cellulose fibers have been generated through etherification under basic water or hydroalcoholic conditions (NaOH/H(2)O/isopropanol). For a given NaOH content, the medium of reaction and, more particularly, the water/IPA ratio, were shown to be of crucial importance to derivatize the fibers without altering their integrity and their crystalline nature. It was shown that the degree of substitution (DS) of the fibers increases concomitantly with isopropanol weight ratio and that, contrary to water or water-rich conditions, derivatization of fibers under isopropanol-rich conditions induces an alteration of the fibers. Optimization of etherification conditions in aqueous media afforded functionalized cellulose materials with DS up to 0.20. Raman confocal microscopy on derivatized fibers cross sections stressed that alkyne moieties are incorporated all over the fibers. The resulting fibers were postfunctionalized by molecular probes and macromolecules in aqueous or water-rich conditions. The effectiveness of the grafting was strongly impacted by the nature of the coupling agents.

LipoParticles: a lipid membrane coating onto polymer particles to enhance the internalization in osteoblast cells.

LipoParticles, core-shell assemblies consisting of a polymer core coated by a lipid membrane, are promising carriers for drug delivery applications with intracellular targets. This is of great interest since it is actually challenging to treat infections involving intracellular bacteria such as bone and joint infections where the bacteria are hidden in osteoblast cells. The present work reports for the first time to the best of our knowledge the proof of enhanced internalization of particles in osteoblast cells thanks to a lipid coating of particles (= LipoParticles). The ca. 300 nm-sized assemblies were elaborated by reorganization of liposomes (composed of DPPC/DPTAP 10/90 mol/mol) onto the surface of poly(lactic-co-glycolic acid) (PLGA) particles, and were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and zetametry. Optimization of these assemblies was also performed by adding poly(ethylene glycol) (PEG) chains on their surface (corresponding to a final formulation of DPPC/DPTAP/DPPE-PEG5000 8/90/2 mol/mol/mol). Interestingly, this provided them colloidal stability after their 20-fold dilution in PBS or cell culture medium, and made possible their freeze-drying without forming aggregates after their re-hydration. Their non-cytotoxicity towards a human osteoblast cell line (MG63) was also demonstrated. The enhanced internalization of LipoParticles in this MG63 cell line, in comparison with PLGA particles, was proven by observations with a confocal laser scanning microscope, as well as by flow cytometry assays. Finally, this efficient internalization of LipoParticles in MG63 cells was confirmed by TEM on ultrathin sections, which also revealed localization close to intracellular Staphylococcus aureus.

Mixed-Matrix Membranes Based on Polyetherimide, Metal-Organic Framework and Ionic Liquid: Influence of the Composition and Morphology on Gas Transport Properties.

In this work, membranes based on polyetherimide (PEI), a ZIF-8 metal-organic framework and 1-ethyl-methylimidazolium tetrafluoroborate ionic liquid (IL) were prepared. IL and ZIF-8 contents amounting to 7 wt% and 25 wt%, respectively, were investigated. CO2, He and H2 transport properties of PEI/IL/ZIF-8 membranes were compared to those obtained for the respective PEI/ZIF-8 and PEI/IL systems. Membranes' gas permeability and selectivity are discussed as a function of the membrane composition and morphology, and they were assessed in relation to existing experimental and theoretical data from the literature. Promising gas transport properties were obtained using the appropriate combination of ZIF-8 and IL amounts in the PEI matrix. Indeed, an increase in the CO2 permeability coefficient by a factor of around 7.5 and the He and H2 permeability coefficients by a factor of around 4 was achieved by adding 7 wt% IL and 10 wt% ZIF-8 to the PEI matrix. Moreover, diffusion was evidenced as a governing factor in the studied membrane series.

Cytocompatibility / Antibacterial Activity Trade-off for Knittable Wet-Spun Chitosan Monofilaments Functionalized by the In Situ Incorporation of Cu2+ and Zn2.

The wet spinning of cytocompatible, bioresorbable, and knittable chitosan (CTS) monofilaments would be advantageous for a variety of surgical applications. The complexation capacity of chitosan with Cu2+ or Zn2+ can be leveraged to enhance its antibacterial activity, but not at the expense of cytocompatibility. In this work, a wet-spinning process was adapted for the in situ incorporation of Cu2+ or Zn2+ with chitosan dopes to produce monofilaments at different drawing ratios (τtot) with various cation/glucosamine molar ratios, evaluated in the fibers (rCu,f and rZn,f). Cytocompatibility and antibacterial activity of wet-spun monofilaments were, respectively, quantified by in vitro live-dead assays on balb 3T3 and by different evaluations of the proliferation inhibition of Staphylococcus epidermidis (Gram+) and Escherichia coli (Gram-). Knittability was tested by a specific tensile test using a knitting needle and evaluated with an industrial knitting machine. It was found that rCu,f = 0.01 and rZn,f = 0.03 significantly increase the antibacterial activity without compromising cytocompatibility. Wet spinning with τtot = 1.6 allowed the production of knittable CTS-Cu monofilaments, as confirmed by knitting assays under industrial conditions.

Micron range morphology of physical chitosan hydrogels.

Physical chitosan hydrogels are potential biomaterials for several biomedical applications, such as wound healing, tissue repair, and drug delivery. Controlling the microstructural organization of chitosan gels is one of the keys for monitoring the physical, mechanical, and biological properties. As a result, the main objective of the present work was to explore the microstructural organization of chitosan hydrogels in relation with the processing conditions of gelation. For this purpose, different gelation routes were studied, that is, chitosan solution neutralization of an aqueous or hydroalcoholic solution and neutralization of an alco-gel. Overall, the resulting morphology after processing was determined by the medium viscosity during neutralization and the nature and concentration of the base. The effect of these processing parameters on the morphology was evaluated mainly through small angle light scattering (SALS) measurements including in situ measurements during chitosan neutralization. As a result, we reported different bulk microstructures consisting in 200-400 nm aggregates (primary particles) agglomerated into micrometer range clusters or arranged into more organized structures, that is, forming microchannels (4-6 µm). We thus established a qualitative and quantitative relation between supramolecular morphology and gelation conditions of chitosan hydrogels.

Continuum of structural organization from chitosan solutions to derived physical forms.

The structural organization of chitosan, a cationic polyelectrolyte, in aqueous solutions of high ionic strength, is investigated by quasi-elastic light scattering and wet scanning transmission electron microscopy. The formation of submicrometric chain aggregates driven by hydrophobic interactions is evidenced. These heterogeneities are at the core of the multiscale morphology of physical hydrogels processed from this polysaccharide. Therefore, a close structural relationship exists between the initial solution and the final hydrogel.

The morphology of rigid polyurethane foam matrix and its evolution with time during foaming - New insight by cryogenic scanning electron microscopy.

This paper presents an investigation of the morphology of growing polyurethane (PU) rigid foams during the very first seconds of the process by cryogenic scanning electron microscopy (cryo-SEM) performed at -150 °C. The heterogeneous nature of the initial mixture has been revealed with the presence of sub-micron size physical blowing agent droplets (isopentane), µm size dispersed phase nodules, and large air bubbles dispersed in a continuous matrix. Following the evolution of the microstructure during foaming by cryo-SEM suggested that the isopentane liquid droplets (undissolved part of the physical blowing agent) did not vaporize to create their own bubbles. These observations were confirmed by showing that the number of air bubbles per unit volume (∼106 bubble/cm3) was similar to the cell population density of the final foam (∼106 cell/cm3), while the number of isopentane droplets initially present was found to be six orders of magnitude higher (∼1012 droplet/cm3). This all means that isopentane molecules initially dissolved in the continuous phase diffuse into the pre-existing air bubbles with no energy barrier to overcome (non-classical nucleation) whereas the isopentane droplets simply act like reservoirs. Finally, despite our best efforts, there is still some doubt whether polymeric 4,4-diphenylmethane diisocyanate (PMDI) is dispersed in the polyol phase, or polyol dispersed in PMDI.

Polyether Sulfone-Based Epoxy Toughening: From Micro- to Nano-Phase Separation via PES End-Chain Modification and Process Engineering.

The toughness of a high-performance thermosetting epoxy network can be greatly improved by generating polyether sulfone-based macro- to nano-scale morphologies. Two polyethersulfones (PES) which only differ by their chain-end nature have been successively investigated as potential tougheners of a high-Tg thermoset matrix based on a mixture of trifunctional and difunctional aromatic epoxies and an aromatic diamine. For a given PES content, morphologies and toughness of the resulting matrices have been tuned by changing curing conditions and put into perspective with PES chain-end nature.

Tuning relaxation dynamics and mechanical properties of polymer films of identical thickness.

Using dewetting as a characterization tool, we demonstrate that physical properties of thin polymer films can be regulated and tuned by employing variable processing conditions. For different molecular weights, the variable behavior of polystyrene films of identical thickness, prepared along systematically altered pathways, became predictable through a single parameter P, defined as the ratio of time required over time available for the equilibration of polymers. In particular, preparation-induced residual stresses, the corresponding relaxation times as well as the rupture probability of such films (of identical thickness) varied by orders of magnitude following scaling relations with P. Our experimental findings suggest that we can predictably enhance properties and hence maximize the performance of thin polymer films via appropriately chosen processing conditions.

Biohybrid cellulose fibers: Toward paper materials with wet strength properties.

Herein, we report on the preparation of novel cellulose-PEG biohybrid papers with wet strength properties. The biohybrid paper sheets are obtained using a two-step procedure where ω- or α, ω-azide functionalized PEG chains are anchored onto alkyne-functionalized wood fibers through CuAAC ligation in mild and aqueous conditions. The incorporation of the PEG grafts mostly occurs at the periphery of the cellulose fibers and degrees of substitution up to 0.028 are obtained. The presence of PEG grafts significantly increases the tensile, burst and tear strength properties in the wet state, the reinforcement being more pronounced for fibers grafted with α,ω-azide PEG. This reinforcement is consistent with a relatively sparse hetero-crosslink reaction creating inter-fiber covalent bonds and forming a cellulose network within the cell wall.

Processing and antibacterial properties of chitosan-coated alginate fibers.

The preparation of chitosan-coated alginate fibers by a wet spin process is presented and the characterization of the antibacterial activities of these fibers is discussed. Preformed calcium alginate fibers were passed in chitosan acetate solutions. The coagulation method of the coating consisted in the immersion of fibers in a bath of calcium dihydroxide solution (0.1 M). The antibacterial evaluation was achieved by a CFU (Colony-Forming Units) counting method after 6 h of incubation at 37 °C. The incorporation of chitosan on calcium alginate fibers brings antibacterial activities against Staphylococcus epidermidis, Escherichia coli and various Staphylococcus aureus strains namely MSSA (Methicillin Sensitive Staphylococcus aureus), CA-MRSA (Community Associated Methicillin Resistant Staphylococcus aureus) and HA-MRSA (Healthcare Associated Methicillin Resistant Staphylococcus aureus) which make these chitosan-coated fibers potential candidates for wound dressing materials. Developing a wound dressing with the haemostatic and healing properties of alginate combined with antibacterial properties of chitosan is envisioned for fighting against the infections and more particularly nosocomial diseases.

Modular construction of single-component polymer nanocapsules through a one-step surfactant-free microemulsion templated synthesis.

Formation of O/W surfactant-free microemulsions from water/oil/acetone ternary systems is exploited to construct precisely-defined shell-functionalized core-loaded nanocapsules with tunable diameters (ranging from 50 to 190 nm) in one step.