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[Display omitted] Polymerization-induced self-assembly (PISA) is an emerging platform technology offering many advantages to produce polymeric nano-objects compared to the solvent switch methods. Aqueous dispersion reversible addition fragmentation chain transfer PISA (aqueous dispersion RAFT PISA) has progressively won over many research groups due to its green chemical process and amazing efficiency to produce a wide range of morphologies. This review summarizes the recent works reported in the literature on the aqueous dispersion RAFT PISA. After a general introduction on the PISA process, exhaustive lists of the different RAFT activation techniques, the hydrophilic steric stabilizers, and the monomers used are shown and discussed. Our objective is to provide an overview for experts and a toolbox for nonexperts that aim to explore this robust and efficient route to produce block copolymer-based nano-objects for a specific application. [ABSTRACT FROM AUTHOR]

Purpose: Despite the promising applications of PLGA based particles, studies examining the fate and consequences of these particles after intra-articular administration in the joint are scanty. This study was carried out to evaluate the neutrality of the unloaded delivery system on different articular cell types. To facilitate tracking, we have thus developed a fluorescent core of particles, combined to a hyaluronate shell for cell recognition. Methods: Fluorescence pictures were taken at time intervals to assess the internalization and the corresponding inflammatory response was monitored by RT-qPCR and biochemical measurements. After NPs pre-treatment, mesenchymal stem cells (MSCs) were cultured into chondrogenic, adipogenic or osteogenic differentiation media, to investigate if NPs exposure interferes with differentiation ability. Finally, intra-articular injections were performed in healthy rat knees and joint's structure analysed by histological studies. Results: Particles were detected in cytoplasm 8 h after exposure. Internalization led to a slight and reversible increase of inflammatory markers, but lower than in inflammatory conditions. We have confirmed particles exposure minimal neutrality on MSCs pluripotency. Histological exams of joint after intra-articular injections do not demonstrate any side effects of NPs. Conclusions: Our findings suggest that such a delivery platform is well tolerated locally and could be used to deliver active molecules to the joint. [ABSTRACT FROM AUTHOR]

Protein C-loaded nanoparticles coated with monomethoxypoly (ethylene oxide) (MPEO) were prepared by double emulsion/solvent evaporation using water-soluble biocompatible copolymers of MPEO and polylactide, as surfactants of the secondary emulsion. The nanoparticle preparation was optimized to obtain the best yield of encapsulated protein C and provide the greatest retention of its biological activity. The nanoparticles were characterized in terms of size, zeta potential, and thickness of the MPEO external layer. Protein C-loaded nanoparticles were injected into the bloodstream of guinea pigs and the protein concentration in plasma is measured as a function of time. After a rapid release corresponding to 20% of the injected protein, the protein plasma concentration progressively decreased and reached a value close to zero after 5 h. Consequently, the in vivo fate of the fluorescent nanoparticles coated with or without MPEO is studied. The uncoated nanoparticles were rapidly captured by the circulating granulocytes while the coated ones were not. The histological analysis of the spleen, 1 hour after injection, showed that the MPEO-coated particles were retained in this organ, while the uncoated ones were not captured. [ABSTRACT FROM AUTHOR]

A two‐step synthetic procedure is designed for preparing new flame‐retardant methacrylic monomers containing 9,10‐dihydro‐9‐oxa‐10‐phosphaphenanthrene‐10‐oxide (DOPO) as a substituent side group. DOPO and methacrylate moieties are linked by linear aliphatic hydrocarbon spacers (3 to 11 carbon atoms). Copolymerization with methyl methacrylate is carried out leading to copolymers containing between 2 and 10 wt% phosphorus. All homo‐ and copolymers exhibit a unique glass transition temperature (Tg). A new group contribution for DOPO‐based substituent is extracted that leads to reasonable estimations of Tgs of other published polymers. The Fox equation provides a good estimation of Tgs for most copolymers and for physical blends of poly(methyl methacrylate) (PMMA) and DOPO. When using monomers having three and four carbon atoms in the hydrocarbon spacer, the Tg of copolymers remains close to that of PMMA over a wide range of composition. Phosphorus‐containing methacrylate homo‐ and copolymers containing 9,10‐dihydro‐9‐oxa‐10‐phosphaphenanthrene‐10‐oxide (DOPO) are synthesized and characterized with regard to their glass transition temperature (Tg). A new group contribution of DOPO side group is derived and allows reliable estimations of Tgs of a large number of polymers. DOPO‐containing copolymers exhibit significantly higher Tgs than the corresponding physical blends. [ABSTRACT FROM AUTHOR]

PLA nanoparticles loaded with n -alkyl gallates (AGs) were prepared either by nanoprecipitation (NP) or by O/W emulsion/solvent evaporation (E/SE). A nonionic hydrophobically modified polysaccharide was used for surface coverage and for ensuring colloidal stability. Different parameters were systematically assessed to enhance the drug incorporation, with the aim of obtaining monomodal and narrow particle size distributions. The nanoparticles were characterized by 1 H NMR, transmission electron microscopy (TEM) and laser light scattering granulometry. The colloidal stability of suspensions was evaluated after incubation in NaCl solutions and was maintained up to 1 M NaCl. The mean particle diameter and the width of size distribution were found very similar for both processes (slightly lower diameters when using E/SE) with various drug loadings. The amount of encapsulated AG by E/SE was about twice that encapsulated by NP. The in-vitro release of AG was evaluated under sink conditions and no burst effect was observed. Release curves were successfully modeled using the Fick diffusion model with a constant diffusion coefficient and assuming non-swellable particles. Diffusion coefficients of AG loaded in nanoparticles prepared by NP were higher than those found in nanoparticles elaborated by E/SE. [ABSTRACT FROM AUTHOR]

ABSTRACT Poly( d,l-lactide- co-glycolide) (PLGA) copolyesters are commonly used in biomedical applications. Researches were carried out on nontoxic or low-toxic catalysts that are enough efficient to provide short polymerization times, adequate microstructure chains and similar properties than the commercial PLGA materials. In this study, PLGA were synthesized by ring-opening copolymerization (ROP) using three different catalysts. Stannous octoate is the first catalyst we used, as it is very efficient, even its toxicity is still on debate. Two others low-toxic catalysts [zinc lactate and bismuth subsalicylate (BiSS)] were also evaluated. The comparison of these ROP was realized in terms of kinetics and control of the polymerization. Then, the influence of the catalyst on the PLGA microstructure chains is reported. Finally, abiotic hydrolytic degradation rate is studied. Results described in this article show that BiSS is one very attractive catalyst to produce low toxic PLGA for biomedical applications. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1130-1138 [ABSTRACT FROM AUTHOR]

In this study, Pickering emulsions of dodecane and medium chain triglyceride (MCT) oils were stabilized by simply alkylated-dextran nanoparticles. Our findings show that very little of these bio-friendly nanoparticles is necessary to stabilize Pickering emulsions while providing a high time stability (more than a year at 37 °C). As dextran is known to be cleavable by dextranase enzyme, hydrolysis of the nanoparticles in the presence of dextranase could be achieved. This allowed performing on-demand destabilization of Pickering emulsions. Furthermore, two different fluorescent probes were loaded into the stabilizing particles and the oil droplets respectively, providing a proof of concept for co-encapsulation of actives in advanced delivery applications. Additionally, to a conventional fluorescence probe, quinine, an antimalarial drug was also encapsulated into the nanoparticles. [Display omitted] [ABSTRACT FROM AUTHOR]

To easily perform atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA) in homogeneous medium from unprotected polysaccharidic macroinitiators, the ATRP of MMA carried out in dimethylsulfoxide has been firstly reinvestigated using Cu(I)Br as metal catalyst and ethyl 2-bromoisobutyrate as initiator. Two ligands, 2,2′-bipyridyne (Bpy) and N-( n-propyl)-2-pyridylmethanimine ( n-Pr-PMI), have been compared, as well as the addition of Cu(II)Br (10 molar % relative to Cu(I)Br) or the adjustment of experimental temperature (from 30 to 60 °C). Appropriate conditions were founded for both ligands to achieve a controlled ATRP. Bpy giving far much faster polymerization compared to n-Pr-PMI, n-Pr-MI was preferred as ligand for accurate tuning of the conversion. Experimental procedure was then applied to unprotected macroinitiators based on dextran to obtain amphiphilic poly(methyl methacrylate) grafted dextran. While homopolymerization was controlled in these conditions, parameters have to be adjusted for the hydrophilic unprotected macroinitiators to prevent gel formation and control ATRP. [ABSTRACT FROM AUTHOR]

Abstract: Dextran-covered poly(lactic acid) (PLA) nanoparticles were prepared using the nanoprecipitation process. Two alternative procedures were compared. On the one hand, PLA was nanoprecipitated in the presence of dextran-based polymeric stabilizer. On the other hand, a PLA-grafted dextran copolymer was nanoprecipitated without the addition of any external stabilizer. The characteristics of particles (yield, size, colloidal stability in the presence of salt) were correlated to the properties of initial polymers. PLA-grafted dextran led to small particles, with high yield and improved colloidal stability even without any stabilizer in the aqueous phase. Viscometric experiments in organic solvent/water mixtures indicated that PLA-grafted dextran self-organized upon mutual diffusion of water and organic solvent spontaneously, providing nanoparticles with a PLA core and a dextran-enriched surface. These nanoparticles exhibited good colloidal stability in water even at high ionic strengths (4mol/L). [ABSTRACT FROM AUTHOR]

The synthesis of amphiphilic dextran- g-poly(methyl methacrylate) glycopolymers (Dex- g-PMMA) is studied using 'grafting from' concept and atom transfer radical polymerization. Two strategies have been examined to control the macromolecular parameters of such glycopolymers. One is involving four steps including a protection/deprotection approach and the second one only two steps. The introduction of initiators group onto a protected acetylated dextran (and directly onto dextran) was achieved resulting in protected DexAcBr (and in unprotected DexBr). These two types of polysaccharidic macroinitiators differ in term of solubility (hydrophilic DexBr vs. hydrophobic DexAcBr) and of position of the initiators groups on the glucosidic units (which are the sites of the future grafts). When evaluated as macroinitiators for ATRP of MMA, control was achieved in both cases but DexBr gave much faster polymerization and lower average grafting efficiency compared with DexAcBr or model initiator. Advantages and drawbacks of both pathways have finally been discussed. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010 [ABSTRACT FROM AUTHOR]

Abstract: Surface segregation and restructuring in polylactides (poly(d,l-lactide) and poly(l-lactide)) and poly(d,l-lactide-co-glycolide) (PLGA) films of various thicknesses were investigated using both attenuated total reflection FTIR (ATR-FTIR) and contact angle relaxation measurements. In case of poly(d,l-lactide) (DLPLA), it was observed that the surface segregation and the surface restructuring of methyl side groups are influenced by the polymer film thickness. This result has been confirmed by X-ray photoelectron spectroscopy (XPS). In the same way, PLGA thick films were also characterized by an extensive surface segregation of methyl side groups. Finally, surface restructuring was investigated by dynamic contact angle measurements and it was observed when film surface comes into contact with water. In parallel, we also found that poly(l-lactide) (PLLA) thin and clear films with thickness ∼15μm undergo conformational changes on the surface upon solvent treatment with certain solvents. The solvent treated surface of PLLA becomes hazy and milky white and its hydrophobicity increases compared to untreated surface. FTIR spectroscopic analysis indicated that polymer chains at the surface undergo certain conformational changes upon solvent treatment. These changes are identified as the restricted motions of C–O–C segments and more intense and specific vibrations of methyl side groups. During solvent treatment, the change in water contact angle and FTIR spectrum of PLLA is well correlated. [Copyright &y& Elsevier]

Abstract: We have already shown that polylactide (PLA) nanoparticles covered with a hydrophilic polymeric layer can be prepared by simple emulsion/solvent evaporation by using amphiphilic copolymers as surfactants during the procedure. The external layer is then constituted by the hydrophilic part of the macromolecular surfactant. This kind of nanospheres is useful for the encapsulation of lipohilic molecules. The use of amphiphilic copolymers as surfactants in the preparation of PLA nanospheres with controlled surface properties, was then applied to the double emulsion/solvent evaporation procedure. The aim was to allow the encapsulation of water-soluble bioactive molecules in PLA particles with controlled surface properties. In this paper, we describe the results obtained with three different water-soluble monomethoxypolyethylene oxide (MPEO)-b–PLA diblock copolymers used as surfactants in the preparation of nanoparticles by double emulsion/solvent evaporation. After organic solvent evaporation, the obtained nanospheres were proved to be really covered by a MPEO layer whose characteristics were determined. It was firstly shown that the MPEO-covered particles did not flocculate at 25°C, even in 4M NaCl while suspensions of bare nanospheres were destabilized for a NaCl concentration as low as 0.04M. On the other hand, the suspensions of MPEO-covered nanoparticles in 0.3M Na2SO4 were found to be very sensitive to temperature as they flocculated at a temperature lying between 45 and 55°C depending on the MPEO-b–PLA composition. This property was attributed to the fact that MPEO is a polymer with a low critical solution temperature. The concentration of MPEO at the nanoparticle surface was then calculated for the three kinds of particles, from the initial flocculation temperature, and was found to be comparable to the value determined directly. [Copyright &y& Elsevier]

Abstract: The predominant mechanism of the hydrolytic degradation of oligo(d,l-lactide)-grafted dextrans in phosphate buffer was followed by quantifying both released dextran and lactic acid from the copolymers. The studied amphiphilic copolymers, with well-defined structure, exhibited various oligo(d,l-lactide) weight fractions (F OLA) while having a quite high extent of free hydroxyl groups (>90%). Depending on their F OLA, oligo(d,l-lactide)-grafted dextrans were soluble either in water or in organic solvents (THF, toluene,…) and different prevailing mechanisms of hydrolytic degradation were observed. The copolymer soluble in THF, with longer oligo(d,l-lactide) grafts and higher F OLA, was found to degrade via a particular mechanism by which the greatest part of dextran was released into buffer medium during the first two weeks of degradation. During the initial stage of degradation, the hydrophilicity of dextran backbone was considered to be the main driving force for the hydrolytic cleavage of the ester linkage between backbone and grafts. Released oligo(d,l-lactide) grafts were found to be degraded via chain-end degradation or random degradation depending on their solubility in buffer medium. In case of water-soluble copolymers with shorter oligo(d,l-lactide) grafts and lower F OLA, the chain-end degradation was exclusively observed. [Copyright &y& Elsevier]

[Display omitted] • (Meth)acrylate and acrylamide monomers based on a protected gallic acid are obtained. • Controlled photo-mediated RAFT polymerization of these original monomers was carried. • Polymers with one free gallic acid as lateral substituent per monomer unit are described. • Intrinsic antibacterial and antioxidant properties of these polymers are highlighted. The development of bio-based thermoplastics is rapidly growing due to the depletion of fossil fuel reserves but also in the hope of obtaining polymers with original properties. Herein, we report the controlled synthesis of original homopolymers derived from gallic acid, one of the well-known natural polyphenols that exhibits various health-promoting effects. More precisely, acrylate, methacrylate and acrylamide monomers based on a protected gallic acid are firstly obtained by a rethought multistep scheme. Then, a controlled photo-mediated RAFT (Reversible Addition Fragmentation chain Transfer) polymerization is carried out before a final deprotection. By this way, original polymers bearing a free gallic acid as a lateral substituent on each monomer unit are described. The intrinsic antibacterial and antioxidant properties of these polymers are highlighted and compared with those of gallic acid. [ABSTRACT FROM AUTHOR]

Aiming to prepare oily core pH-sensitive nanocapsules (NCs) for anticancer drugs delivery, the use of a dextran-based transurf (DexN 3- τ CTA γ) as both stabilizer and macromolecular chain transfer agent in methyl methacrylate/2-(diethylamino)ethyl methacrylate (MMA/DEAEMA) miniemulsion copolymerization was investigated. NCs of about 195 nm with an oily-core of Miglyol 810 (M810) and a dextran coverage covalently linked to the poly(MMA- co -DEAEMA) intern shell have been obtained. Compared to the non-sensitive PMMA-based NCs (prepared in a similar way), these novel objects were shown to swell in acidic media and to trigger Coumarin 1 release in physiological relevant pH range. As a starting point of NCs biological effects, cytotoxicity and NCs-proteins interactions studies were performed with both PMMA and poly(MMA- co -DEAEMA)-based NCs. Finally, free azide functions from dextran-based coverage were successfully exploited to attach fluorescent model dyes to NCs surface. The overall results suggest that this novel NCs platform could be potentially used as drug nanocarriers for intravenous injection. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor receptor 2 (TNFR2) is expressed on some tumor cells, such as myeloma, Hodgkin lymphoma, colon cancer and ovarian cancer, as well as immunosuppressive cells. There is increasingly evidence that TNFR2 expression in cancer microenvironment has significant implications in cancer progression, metastasis and immune evasion. Although nanomedicine has been extensively studied as a carrier of cancer immunotherapeutic agents, no study to date has investigated TNFR2-targeting nanomedicine in cancer treatment. From an epigenetic perspective, previous studies indicate that DNA demethylation might be responsible for high expressions of TNFR2 in cancer models. This perspective review discusses a novel therapeutic strategy based on nanomedicine that has the capacity to target TNFR2 along with inhibition of DNA demethylation. This approach may maximize the anti-cancer potential of nanomedicine-based immunotherapy and, consequently, markedly improve the outcomes of the management of patients with malignancy. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Multi-reactive dextran-based inisurfs are used for a minemulsion polymerization. • Inisurfs act as macroinitiators and stabilizers of miniemulsion AGET-ATRP of MMA. • Inisurfs confine the ATRP at oil/water interface which improves its control. • Potentially biocompatible dextran-covered oily-core nanocapsules are produced. • Nanocapsules morphology is achieved only for the largest oil content. Abstract A convenient one-step method is developed to prepare potentially biocompatible nanocapsules (NCs) with a biocompatible oily core (Miglyol 810, M810), a poly(methyl methacrylate) (PMMA) shell and a dextran coverage. For that, a multi-reactive dextran derivative containing both hydrophobic phenoxy and ATRP initiator groups is used as inisurf (macroinitiator and stabilizer) in an Activator Generated by Electron Transfer-Atom Transfer Radical Polymerization (AGET-ATRP) miniemulsion process. Such dextran inisurfs are shown to efficiently stabilize the direct miniemulsion of MMA with M810 as co-stabilizer, and to confine the polymerization at the oil/water interface via their multiple initiator sites. Grafted copolymers are produced from the inisurf, whose grafts constitute the inner polymeric shell of NCs and are linked to the dextran coverage. The confinement of such polymerization at interface is found to reduce initiator group efficiency, but also to improve both polymerization kinetics and control in comparison with one molecular model initiator. Increasing M810 content promotes the oily core/PMMA shell phase separation during polymerization and the formation of slightly larger NCs, without affecting polymerization kinetics. [ABSTRACT FROM AUTHOR]

In this study, the degradation mechanism and tensile properties of plasticized poly(D,L-lactide-co-glycolide) (PLGA) are evaluated. Purasorb PDLG 5010 is first extruded into rods with or without plasticizers, i.e, D,L-lactide or aspirin. Then, the hydrolytic degradation of such rods is studied in phosphate buffer solution. A very fast hydrolytic degradation (half-life time lower than 1 month) that is enhanced by the presence of plasticizer occurs through a heterogeneous mechanism and leads to the formation of hollow rods. The mechanical properties of these rods are studied in dry and wet states. Finally, water diffusivity in plasticized (or not) PLGA is estimated. [ABSTRACT FROM AUTHOR]

Hypothesis For some years, smart nano-objects are one of the main focuses of current research. In the framework of polymeric nanomedicine, o -nitrobenzyl alcohol derivatives lead to light-responsive polymeric materials. At this day, nanomedicine based on polysaccharide/poly( o -nitrobenzyl acrylate) (PNBA) copolymers have never been reported. Experiments For the first time, PNBA core/dextran shell nanoparticles (NPs) were formulated by evaluating two different processes: (i) nanoprecipitation of preformed Dextran-g-PNBA glycopolymers, (ii) emulsion/evaporation using azido-functionalized PNBA and alkynated dextran, carrying out (or not) an interfacial click chemistry reaction. NPs’ characterization, colloidal stability in the presence of salts and of an anionic competitive surfactant (SDS) and light-induced disruption were assessed. Finally, the potential use of these NPs as photo-responsive drug delivery systems was investigated by a preliminary in vitro cytotoxicity study using Caco-2 cells. Findings Whatever the process, the photosensitive property and the colloidal stability of NPs in the presence of salts were proved. However, triazole rings between the dextran shell and the PNBA core avoid the dextran shell desorption in the presence of SDS. NPs' biocompatibility towards Caco-2 was proved and 100% cell viability was still observed after exposure to NPs following by 60 s UV-irradiation. [ABSTRACT FROM AUTHOR]

Ethyl tert -butyl ether (ETBE) is a fuel octane enhancer considered as a major bio-fuel in Europe. Blended with gasoline fuels, ETBE improves fuel combustion and reduces toxic hydrocarbon emissions. ETBE industrial synthesis leads to an azeotropic mixture EtOH/ETBE (20/80 wt%), which cannot be separated by simple distillation. According to former works, cellulose acetate (CA) membranes were extremely selective with a permeate EtOH content of 100% but their flux was too low for ETBE purification by the pervaporation (PV) membrane process. The affinity of the bio-based polylactide (PLA) for ethanol has also been reported for poly(vinyl pyrrolidone)/PLA blends for this application. In this work, new bio-based membranes were obtained by grafting CA with controlled PLA amounts by a “grafting onto” strategy. The CA- g -PLA copolymers were characterized by ATR-FTIR, 1 H NMR, DSC and SAXS. Their membrane properties were investigated in terms of structure-morphology-property relationships for the sorption and pervaporation of the targeted EtOH/ETBE mixture. PLA grafting onto CA strongly improved the flux (×12) while the ethanol permeate content remained in the very high range (C′>90 wt%) for ETBE purification by pervaporation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Dextran-covered nanocapsules (NCs) have been obtained by emulsion-evaporation method coupled with an in situ click Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction occurring at liquid/liquid interface. To assure biocompatibility and biodegradability of NCs, α-alkyne PLA was chosen as inner shell and Miglyol 810 (M810) as oily core. NCs were covered by a hydrophilic superficial layer of dextran modified by azide-terminated 6-carbon aliphatic side chains, so-called DexN 3 . DexN 3 was dissolved in the aqueous phase, but during emulsion process it migrated at the interface to act both as stabilizer and as reactant. Click reaction occurred at the oil-in-water interface between azide functions from DexN 3 and alkyne groups of PLA present in the organic phase. Influence of different parameters, such as catalyst system or sonication conditions, has been studied on CuAAC reaction efficiency. CuSO 4 /AAsc was proven to be the most efficient catalyst. NCs characteristics in terms of particle size distribution, dextran coverage, colloidal stability in presence of salt and of SDS (competitive surfactant) as well as their morphology have been investigated. Core–shell NCs were obtained with various M810 content. Covalent linkages between PLA shell and dextran coverage improved colloidal stability of NCs, even in presence of SDS but also increased dextran density and thickness, in comparison to non-clicked NCs. [ABSTRACT FROM AUTHOR]

Atom Transfer Radical Polymerization (ATRP) and Ring-Opening Polymerization (ROP) were combined to synthesize diblock environmental friendly poly(ϵ-caprolactone)-block-poly(methyl ether diethylene glycol methacrylate) (PCL- b -PMEO 2 MA) through a sequential two-step strategy. These PCL- b -PMEO 2 MA copolymers were produced using 2-hydroxyethyl-2-bromoisobutyrate as bifunctional initiator. In the first step, ϵ-caprolactone was initiated by the hydroxyl group of this particular initiator. Tin octoate, zinc triflate and bismuth triflate were tested as non-toxic catalysts to obtain α-bromide–ω-hydroxy bifunctional PCL macroinitiator. Secondly, the controlled ATRP of MEO 2 MA was tuned from the same bifunctional initiator. Finally, PCL- b -PMEO 2 MA were produced by carrying out ATRP of MEO 2 MA from PCL macroinitiator. Preliminary data on self-assembly of such thermo-sensitive PCL- b -PMEO 2 MA in aqueous phase are given. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT Polymers containing o-nitrobenzyl esters are promising for preparation of light sensitive materials. o-Nitrobenzyl methacrylate has already been polymerized by controlled ATRP or RAFT. Unfortunately, the radical polymerization of o-nitrobenzyl acrylate (NBA) was not controlled until now due to inhibition and retardation effects coming from the nitro-aromatic groups. Recent developments in the Single Electron Transfer-Living Radical Polymerization (SET-LRP) provide us an access to control this NBA polymerization and living character of this NBA SET-LRP is demonstrated. Effects of CuBr2 and ligand concentrations, as well as Cu(0) wire length on SET-LRP kinetics are shown presently. A first-order kinetics with respect to the NBA concentration is observed after one induction period. SET-LRP proceeds with a linear evolution of molecular weight and a narrow distribution. High initiation efficiency close to 1 and high chain-end functionality (∼93%) are reached. Chain extension of poly( o-nitrobenzyl acrylate) is realized with methyl acrylate (MA) to obtain well defined poly( o-nitrobenzyl acrylate)-b-poly(methyl acrylate) (PNBA- b-PMA). Finally, light-sensitive properties of PNBA are checked upon UV irradiation. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2192-2201 [ABSTRACT FROM AUTHOR]

Abstract: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) were formulated into in situ forming implants (ISI) and microparticles (ISM) using PLGA and either N-methyl-2-pyrrolidone (NMP) or triacetin. Physicochemical characterization was carried out, including the study of matrix structure and degradation. A strong correlation between drug hydrophobicity and the in vitro release profiles was observed: whatever the formulation, GSNO and SNAP were completely released after ca. 1day and 1week, respectively. Then, selected formulations (i.e., SNAP-loaded NMP formulations) demonstrated the ability to sustain the vasodilation effect of SNAP, as shown by monitoring the arterial pressure (telemetry) of Wistar rats after subcutaneous injection. Both ISI and ISM injections resulted in a 3-fold extended decrease in pulse arterial pressure compared with the unloaded drug, without significant decrease in the mean arterial pressure. Hence, the results emphasize the suitability of these formulations as drug delivery systems for S-nitrosothiols, widening their therapeutic potential. [Copyright &y& Elsevier]

ABSTRACT A cholesterol-based liquid crystal monomer, diethylene glycol cholesteryl ether acrylate (DEGCholA), has been successfully polymerized by atom transfer radical polymerization (ATRP) for the first time. Appropriate experimental conditions to control the polymerization of DEGCholA have been investigated using a model initiator (ethyl 2-bromoisobutyrate) in tetrahydrofuran (THF) or toluene at 60 °C. Well-controlled ATRP of DEGCholA was obtained using N, N, N′, N′, N″-pentamethyldiethylenetriamine as ligand in THF at 60 °C. These conditions were then applied to initiate the ATRP of DEGCholA from multifunctional macroinitiators based on dextran. Using a protection/deprotection synthetic scheme, novel graft glycopolymers (Dex- g-PDEGCholA) have been synthesized. The mesomorphic properties of DEGCholA, PDEGCholA, and Dex- g-PDEGCholA have been studied by thermal polarizing optical microscopy, differential scanning calorimetry, and X-ray scattering. PDEGCholA and Dex- g-PDEGCholA show an interdigitated smectic A phase (SmAd) between Tg (∼30 °C) and around 170 °C. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3829-3839 [ABSTRACT FROM AUTHOR]

This study aims to investigate the in vitro degradation of a poly(L-lactic-co-glycolic acid)-poly(L-lactic-co-E-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. [ABSTRACT FROM AUTHOR]

Abstract: Aliphatic hydrocarbon oil-in-water nanoemulsions were prepared using mixtures of an amphiphilic nonionic polysaccharide (dextran modified by covalent attachment of hydrocarbon tails) and tetraethylene glycol dodecylether as stabilizers. Nanoemulsions stabilized by amphiphilic polysaccharide alone underwent Ostwald ripening. On the contrary, nanoemulsions prepared with certain mixtures of hydrophobically modified dextran and tetraethylene glycol dodecylether exhibited no significant variation of their average droplet diameter over a period of time that depended strongly on the nature of the dispersed oil. When changing from n-hexane to n-octane and n-dodecane, the period of complete inhibition of Ostwald ripening varied from 3h to several months. Polymer–surfactant interactions and co-adsorption at oil/water interface were demonstrated by dynamic interfacial tension measurements and dilational surface rheology. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Tissue engineering offers an interesting alternative to current anterior cruciate ligament (ACL) surgeries. Indeed, a tissue-engineered solution could ideally overcome the long-term complications due to actual ACL reconstruction by being gradually replaced by biological tissue. Key requirements concerning the ideal scaffold for ligament tissue engineering are numerous and concern its mechanical properties, biochemical nature, and morphology. This study is aimed at predicting the morphology of a novel scaffold for ligament tissue engineering, based on multilayer braided biodegradable copoly(lactic acid-co-(e-caprolactone)) (PLCL) fibers The process used to create the scaffold is briefly presented, and the degradations of the material before and after the scaffold processing are compared. The process offers varying parameters, such as the number of layers in the scaffold, the pitch length of the braid, and the fibers' diameter. The prediction of the morphology in terms of pore size distribution and pores interconnectivity as a function of these parameters is performed numerically using an original method based on a virtual scaffold. The virtual scaffold geometry and the prediction of pore size distribution are evaluated by comparison with experimental results. The presented process permits creation of a tailorable scaffold for ligament tissue engineering using basic equipment and from minimum amounts of raw material. The virtual scaffold geometry closely mimics the geometry of real scaffolds, and the prediction of the pore size distribution is found to be in good accordance with measurements on real scaffolds. The scaffold offers an interconnected network of pores the sizes of which are adjustable by playing on the process parameters and are able to match the ideal pore size reported for tissue ingrowth. The adjustability of the presented scaffold could permit its application in both classical ACL reconstructions and anatomical double-bundle reconstructions. The precise knowledge of the scaffold morphology using the virtual scaffold will be useful to interpret the activity of cells once it will be seeded into the scaffold. An interesting perspective of the present work is to perform a similar study aiming at predicting the mechanical response of the scaffold according to the same process parameters, by implanting the virtual scaffold into a finite element algorithm. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the toxicity of nanoparticles of poly(D,L-lactic acid) (PLA) or poly(D,L-lactic-co-glycolic acid) (PLGA) covered by chemically esterified amphiphilic hyaluronate (HA) which will be used for intra-articular injection as a drug carrier for the treatment of arthritis (RA) and/or osteoarthritis (OA). PLA and PLGA are FDA approved polymers that are already used for the preparation of nano or microparticles. HA is a natural polysaccharide already present in the articulations known to interact with the CD44 receptors of the cells (especially chondrocytes). Therefore, we can envisage that the HA covering can improve the interactions between the cells and the nanoparticles, leading to better targeting or biodistribution. The knee of healthy male rats was injected one to two times weekly, with various concentrations of nanoparticles encapsulating Dextran-FITC. The synovial membranes and the patellae were collected aseptically and histologically analyzed to assess the effects and localization of the nanocapsules in the knee joint. We did not observe significant modifications in the synovial membranes (weak hyperplasia) or patellae integrity after local administration of nanodevices into the rats. While we found some nanoparticles in the synovial membrane, none were detected in the patellae. Moreover, the histological observations for patellae were confirmed by radiosulfate intake, which depicted no decrease in proteoglycans biosynthesis in nanoparticles treated animals. Concerning the safety towards synovial membranes, we also had a look at the inflammatory response after injections of nanoparticles covered by amphiphilic HA or polyvinyl alcohol (PVA) by monitoring the mRNA expression levels of some specific early cytokines (IL-1β and TNF-α). Once again, no differences were observed between the control rats and the rats treated with nanoparticles. Considering these preliminary results obtained in healthy rats, we can establish that neither the amphiphilic HA-covered PLGA nanoparticles nor their degradation products induce major modifications of articular tissues functions, while injected into the knee of healthy rats. These results should be confirmed in OA or RA rat models, in order to confirm that nanoparticles do not worsen already altered (degenerative or inflamed) articular tissues. Once confirmed, such tuneable nanoparticles could be proposed as a safe drug delivery system for the treatment of articular disease, allowing a wide range of encapsulating molecules. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of biodegradable PLA-grafted amylose copolymers has been achieved in three steps to control their architecture as best as possible. First, amylose was partially protected with various silylating agents, especially N,O-bis-(trimethylsilyl)acetamide (BSA). The influence of the silylating agent chemistry and of the BSA/OH molar ratio on the protection yield have been investigated. Furthermore, the reactivity order of the different OH functions towards silylation has been evaluated. The second step is based on the “grafting form” strategy: polylactide (PLA) grafts were generated by the Ring Opening Polymerization (ROP) of d,l-lactide from the free remaining OH groups carried by the partially silylated amylose. Finally, the silylether groups cleavage was tested under various conditions to obtain the PLA-grafted amylose (A-g-PLA), while avoiding backbone and grafts degradation. In addition, two polyelectrolytes, i.e., LiCl and NaNO3 have been used to facilitate the SEC analysis of native amylose. [Copyright &y& Elsevier]

Polysaccharide coated nanoparticles represent a promising class of environmentally friendly latex to replace those stabilized by small toxic molecular surfactants. We report here an in situ formulation of free-surfactant core/shell nanoparticles latex consisting of dextran-based diblock amphiphilic copolymers. The synthesis of copolymers and the immediate latex formulation were performed directly in water using a photo-initiated reversible addition fragmentation chain transfer-mediated polymerization induced self-assembly strategy. A hydrophilic macromolecular chain transfer-bearing photosensitive thiocarbonylthio group (eDexCTA) was first prepared by a modification of the reducing chain end of dextran in two steps: (i) reductive amination by ethylenediamine in the presence of sodium cyanoborohydride, (ii) then introduction of CTA by amidation reaction. Latex nanoparticles were then formulated in situ by chain-extending eDexCTA using 2-hydroxypropyl methacrylate (HPMA) under 365 nm irradiation, leading to amphiphilic dextran-b-poly(2-hydroxypropyl methacrylate) diblock copolymers (DHX). Solid concentration (SC) and the average degree of polymerization -   X n ˉ - of PHPMA block (X) were varied to investigate their impact on the size and the morphology of latex nanoparticles termed here SCDHX. Light scattering and transmission electron microscopy analysis revealed that SCDHX form exclusively spherical nano-objects. However, the size of nano-objects, ranging from 20 nm to 240 nm, increases according to PHPMA block length. [ABSTRACT FROM AUTHOR]

The four‐step synthesis of amphiphilic glycopolymers associating dextran as backbone and poly(methyl methacrylate) (PMMA) as grafts is reported, using the "grafting from" strategy. In the first step, the dextran OH functions were partially acetylated. The second step consisted in linking initiator groups by reaction of 2‐bromoisobutyryl bromide (BiBB) with the unprotected OH functions. Third, the atom transfer radical polymerization (ATRP) of methyl methacrylate was carried out in DMSO from the resulting dextran derivative used as a macroinitiator. Finally, the cleavage of the acetate groups led to the expected glycopolymers. Careful attention was given both to the copolymer structure and the control of polymerization. PMMA grafts were analyzed by SEC‐MALLS after their deliberate cleavage from the backbone to evidence a controlled polymerization. Moreover, the mildness of the final deprotection conditions was proved to ensure acetate cleavage without either degrading dextran backbone and PMMA grafts or cleaving grafts from dextran backbone. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7606–7620, 2008 [ABSTRACT FROM AUTHOR]

The silylation reaction of dextran with 1,1,1,3,3,3-hexamethyldisilazane (HMDS) in DMSO was studied as the first step of the synthesis of new amphiphilic polyester-grafted dextrans. According to the experimental conditions, i.e. dextran molar weight, medium temperature and reaction time, HMDS/OH ratio, addition of a catalyst and co-solvent, partially or totally silylated dextrans were recovered. The highest silylation yields were obtained with the lowest molecular weight dextrans. The increase in temperature medium and/or reaction time, the presence of catalyst or co-solvent favored the protection yield. Whatever the dextran used, complete silylation of the polysaccharide chain could be achieved by adequate selection of the experimental conditions. The thermal properties of resulting silylated polysaccharides were investigated by temperature modulated DSC. It was observed that Tg values of partially silylated dextran were maintained between 120 and 140 °C, independently of the dextran molecular weight. Interestingly, DMSO proved to behave as an efficient plasticizer of (partially) silylated dextrans. The partially silylated dextrans were efficiently used as multifunctional macroinitiators for the controlled ring-opening polymerization (ROP) of lactone. The ROP was then promoted from the remaining hydroxyl groups in the presence of tin or aluminium activator. After polymerization and ultimate deprotection of the silylated dextran backbone, amphiphilic polyester-grafted dextrans were readily recovered. [Copyright &y& Elsevier]

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which emerged in December 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic, took the world by surprise with an unprecedented public health emergency. Since this pandemic began, extraordinary efforts have been made by scientists to understand the pathogenesis of COVID-19, and to fight the infection by providing various preventive, diagnostic and treatment opportunities based on either novel hypotheses or past experiences. Despite all the achievements, COVID-19 continues to be an accelerating health threat with no specifically approved vaccine or therapy. This review highlights the recent advances in COVID-19 infection, with a particular emphasis on nanomedicine applications that can help in the development of effective vaccines or therapeutics against COVID-19. A novel future perspective has been proposed in this review based on utilizing polymersome nano-objects for effectively suppressing the cytokine storm, which may reduce the severity of COVID-19 infection. [ABSTRACT FROM AUTHOR]

• Multi-reactive Dextran-based transurfs (RAFT agent and surfactant) are designed. • Dithiobenzoate groups of transurf confine RAFT polymerization at o/w interface. • RAFT miniemulsion polymerization of MMA from transurf is controlled. • Dextran-covered nanocapsules with PMMA shell and oily core are produced. • Nanocapsules seem to be cytocompatible with vascular smooth muscle cells. A multi-reactive polysaccharide-based transurf (acting both as macro-Chain Transfer Agent and stabilizer) was used to confine RAFT polymerization of methyl methacrylate (MMA) at the oil/water (o/w) miniemulsion interface. Dithiobenzoate groups and hydrophobic aliphatic side chains were introduced onto dextran, conferring it both transfer agent properties and ability to stabilize direct miniemulsion of MMA in the presence of a biocompatible oil, used as co-stabilizer. Because of their amphiphilic character, transurfs were initially adsorbed at the (o/w) interface and their reactive sites mediated RAFT polymerization via the R-group approach. PMMA-grafted dextran glycopolymers were consequently produced at the o/w interface, thus leading to dextran coverage/PMMA shell/oily core nanocapsules (NCs) as evidenced by Cryo-TEM analyses. The influence of dextran-based transurf chemistry and oil amount on MMA RAFT polymerization control was investigated. Positive preliminary results on NCs cytotoxicity suggest the potential of these objects for biomedical applications. [ABSTRACT FROM AUTHOR]

• Photo-sensitive nanoparticles were formulated using two processes. • Two model molecules (Nile Red and Doxorubicin) were encapsulated. • Improved release of such model molecules was easily observed upon UV irradiations. • A stepped release of such model molecules may easily be obtained. In this work, photo-sensitive core/shell nanoparticles (NPs) based on biocompatible dextran- g -poly(o -nitrobenzyl acrylate) copolymers (Dex- g -PNBA), containing dextran as hydrophilic backbone and PNBA as photosensitive grafts, were formulated using two processes. In the first process (nanoprecipitation), NPs were prepared using preformed Dex- g -PNBA copolymers. Using the second process (emulsion/organic solvent evaporation), "clicked" or "unclicked" NPs were obtained carrying out (or not) an interfacial in situ click chemistry, respectively. Two model molecules, Nile Red (NR) and Doxorubicin (DOX), were encapsulated and their controlled release from NPs was investigated under UV irradiations to demonstrate the high potential of such photosensitive NPs in biomedicine applications as drug delivery nanocarriers. According to such irradiations, improved release was easily observed. Release kinetics depended on the formulation process and the NPs core chemistry, but not on the occurrence of the interfacial in situ click chemistry. More interesting, a stepped release of such model molecules may easily be obtained. [ABSTRACT FROM AUTHOR]

From a set of around 100 phosphorus-containing polymers tested in pyrolysis–combustion flow calorimetry, the contributions to flammability of two phosphorus-containing pendant groups (called 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) and PO3) were calculated using an advanced method previously proposed and validated. The flammability properties include total heat release (THR) and heat release capacity (HRC) measured in standard conditions, i.e., anaerobic pyrolysis and complete combustion. The calculated contributions are in good agreement with the main modes of action of both phosphorus groups, i.e., flame inhibition for DOPO and char promotion for PO3. Moreover, the results provide first conclusions about the cooperative interaction between phosphorus and nitrogen, as well as the influence of the architecture of tested co-polymers. [ABSTRACT FROM AUTHOR]

The article presents a study which discusses adhesion and colonization of mesenchymal stem cells on polylactide or PLCL fibers dedicated for tissue engineering. Topics discussed include use of porcine mesenchymal stem cells (MSC) in the study, cultivation and cell adhesion of mesenchymal stem cells, and cultivation of MSC on various polymers such as polymers made with lactic acid or caprolactone.