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The biocompatibility, tunable degradability and broad functionalities of polyphosphoesters and their potential for biomedical applications have stimulated a renewed interest from Chemistry, Medicinal Chemistry and Polymer Sciences. Commercial applications of polyphosphoesters as biomaterials are still hampered because of the time and resource-intensive sourcing of their corresponding monomers, in addition to the corrosive and sensitive nature of their intermediates and by-products. Here, we present a groundbreaking challenge for sourcing the corresponding cyclic phosphate monomers by a different approach. This approach relies on the use of continuous flow technologies to intensify the end-to-end preparation of cyclic phosphate monomers with a semi-continuous modular flow platform. The applied flow technology mitigates both safety and instability issues related to the more classical production of cyclic phosphate monomers. The first flow module allows safe synthesis of a library of cyclic chlorophosphite building blocks and features in-line P-31 NMR real-time monitoring. After optimization on the microfluidic scale, this first module is successfully transposed toward mesofluidic scale with a daily throughput of 1.88 kg. Downstream of the first module, a second module is present, allowing the quantitative conversion of cyclic chlorophosphites with molecular oxygen toward chlorophosphate derivatives within seconds. The two modules are concatenable with a downstream semi-batch quench of intermediate chlorophosphate with alcohols, hence affording the corresponding cyclic phosphate monomers. Such a continuous flow setup provides considerable unprecedented advantages to safely and efficiently synthesize a library of versatile high value-added cyclic phosphate monomers at large scale. These freshly produced monomers can be successfully (co)polymerized, using either batch or flow protocols, into well-defined polyphosphoesters with assessed thermal properties and cytotoxicity.

The synthesis and properties of hybrid poly(ε-caprolactone) (PCL)–poly(ethylene oxide) (PEO) covalent adaptable networks have been investigated.

Introduction: We hypothesised that the active targeting of αvβ3 integrin overexpressed in neoangiogenic blood vessels and glioblastoma (GBM) cells combined with magnetic targeting of paclitaxel- and SPIO-loaded PLGA-based nanoparticles could improve accumulation of nanoparticles in the tumour and therefore improve the treatment of GBM. Methods: PTX/SPIO PLGA nanoparticles with or without RGD-grafting were characterised. Their in vitro cellular uptake and cytotoxicity was evaluated by fluorospectroscopy and MTT assay. In vivo safety and anti-tumour efficacy of different targeting strategies were evaluated in orthotopic U87MG tumour model over multiple intravenous injections. Results: The nanoparticles of 250 nm were negatively charged. RGD targeted nanoparticles showed a specific and higher cellular uptake than untargeted nanoparticles by activated U87MG and HUVEC cells. In vitro IC50 of PTX after 48 h was ∼1 ng/mL for all the PTX-loaded nanoparticles. The median survival time of the mice treated with magnetic targeted nanoparticles was higher than the control (saline) mice or mice treated with other evaluated strategies. The 6 doses of PTX did not induce any detectable toxic effects on liver, kidney and heart when compared to Taxol. Conclusion: The magnetic targeting strategy resulted in a better therapeutic effect than the other targeting strategies (passive, active).

Antimicrobial peptide loaded poly(2-hydroxyethyl methacrylate) particles were synthesized in supercritical carbon dioxide via one-pot free-radical dispersion polymerisation of 2-hydroxyethyl methacrylate and a cross-linker. Discrete particles with a well-defined spherical morphology and a diameter as low as 450 nm have been obtained in mild conditions. The encapsulation and release of the peptide were confirmed by antimicrobial tests that demonstrated for the first time a sustained release of the peptide from poly(2-hydroxyethyl methacrylate) microgels prepared by one-pot dispersion polymerization in supercritical carbon dioxide and then dispersed in water.

Polymer micelles have emerged as promising carriers for controlled release applications, however, several limitations of micelle-based drug delivery have also been reported. To address these issues, we have synthesized a functional biodegradable and cytocompatible block copolymer based on methoxypoly(ethyleneglycol)-b-poly(ε-caprolactone-co-α-azido-ε-caprolactone) (mPEG-b-poly(εCL-co-αN3εCL)) as a precursor of reduction sensitive core-crosslinked micelles. The synthesized polymer was formulated as micelles using a dialysis method and loaded with the anti-inflammatory and anti-cancer drug methotrexate (MTX). The micellar cores were subsequently crosslinked at their pendant azides by a redox-responsive bis(alkyne). The size distributions and morphology of the polymer micelles were assessed using dynamic light scattering (DLS) and transmission electron microscopy, and drug release assays were performed under simplified (serum free) physiological and reductive conditions. Cellular uptake studies in human breast cancer cells were performed using Oregon-green loaded core-crosslinked micelles. The MTX-loaded core-crosslinked micelles were assessed for their effects on metabolic activity in human breast cancer (MCF-7) cells by evaluating the reduction of the dye MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The apoptosis inducing potential of MTX-loaded core-crosslinked micelles was analysed using Hoechst/propidium iodide (PI) and annexin-V/PI assays. The data from these experiments indicated that drug release from these cross-linked micelles can be controlled and that the redox-responsive micelles are more effective carriers for MTX than non-crosslinked analogues and the free drug in the cell-lines tested.

Sulindac loaded poly(HEMA) cross-linked microparticles were synthesized via one-pot free-radical dispersion polymerisation in supercritical carbon dioxide (scCO2) in presence of photocleavable diblock stabilisers based on polyethylene oxide (PEO) and poly(heptadecafluorodecyl acrylate) (PFDA) bearing a o-nitrobenzyl photosensitive junction (hv) (PEO-hv-PFDA), and ethylene glycol dimethacrylate (EGDMA) as cross-linker. Poly(HEMA) cross-linked microparticles either empty or sulindac loaded were obtained with well-defined spherical morphology with the sizes between 250 and 350 nm. Additionally, upon UV-photolysis the stabiliser on the surface was cleaved which permits to microparticles to be redispersed in water leading to water swollen microgels about 2.1–3.6 µm. Moreover, the release behaviour from obtained microgels indicated the sustained release of sulindac over 10 days. Besides, the surface modification after UV-photolysis was studied and proved that the particles can be functionalised with further chemistries.

Poly(ethylene oxide)-b-polyphosphoester amphiphilic block copolymers are known to self-assemble into polymer micelles when dissolved in water. This work aims at reporting on the improvement of the stability of the micelles at high dilution by crosslinking the hydrophobic polyphosphoester micellar core. Typically, an unsaturated alkene side-chain was introduced onto the cyclic phosphate monomer according to a one-step reaction followed by its organocatalyzed polymerization initiated by a poly(ethylene oxide) macroinitiator. This strategy avoids the use of any organometallic compounds in order to facilitate the purification and meet the stringent requirements of biomedical applications. After self-assembly in water, the micelles were cross-linked by simple UV irradiation. These cross-linked micelles have then been loaded with doxorubicin to evaluate their potential as drug nanocarriers and monitor the impact of crosslinking on the release profile.

Poly(ethylene oxide) (PEO)-b-polyphosphate copolymers made of hydrophilic PEO and hydrophobic polyphosphates are amphiphilic copolymers prone to self-assemble in water into nanoparticles. In this work, nanoparticles are obtained by the self-assembly of PEO-b-polyphosphate copolymers in water in the absence of any organic co-solvent whatever the length of the pendant alkyl chain (between 4 and 7 carbon atoms) of the polyphosphate block. Remarkably, this solvent-free process remains efficient even for the most hydrophobic polyphosphate blocks. The critical aggregation concentration (CAC) of the block copolymers was determined by pyrene probe fluorescence. Finally, the efficiency of these copolymer surfactants to decrease the air-water interface was measured by air-bubble tensiometry.

In this paper, we present a small (25×25×3 mm3) power module that integrates two silicon-carbide (SiC) JFETs to form an inverter leg. This module has a “sandwich” structure, i.e. the power devices are placed between two ceramic substrates, allowing for heat extraction from both sides of the dies. All interconnects are made by silver sintering, which offers a very high temperature capability (the melting point of pure silver being 961 °C). The risk of silver migration is assessed, and we show that Parylene-HT, a dielectric material that can sustain more than 300 °C, can completely coat the module, providing adequate protection.

International audience; Silver sintering is a promising alternative to high melting point (HMP) solders which contain lead. Indeed, it offers better thermal and electrical properties, and can operate at higher temperature. However, silver tends to migrate in presence of electric field, oxygen (or moisture) and high temperature, causing short circuits. In this paper, we assess the extend of this issue, and we evaluate the protective effect of a thin layer of parylene. It is shown that silver migration occurs rapidly (tens to hundred of hours at 300°C), but that parylene offers a good mitigation of this issue.

National audience; Silver sintering is a promising alternative to high melting point (HMP) solders which contain lead. Indeed, it offers better thermal and electrical properties, and can operate at higher temperature. Currently, several implementations of this technique are available, based on various silver particles sizes and sintering additives. This paper presents a review of the different implementations, and gives practical details about one of them, based on silver nanoparticles. One specific aspect is highlighted: the metal finish of the DBC substrate. It has a major impact on the quality of the sintered joint: with some finishes, the adhesion is excellent (more than 50 MPa), while it is poor with some others (lower than 10 MPa).

International audience; Silicon Carbide (SiC) Junction-Field Effect Transistors (JFETs) are attractive devices for power electronics. Their high temperature capability should allow them to operate with a reduced cooling system. However, experiments described in this paper conclude to the existence of runaway conditions in which these transistors will reach destructive temperatures.

International audience; With the emergence of new power semiconductor devices, the switching speeds in power converters are increasing. The stray inductances of switching cells must therefore be minimized to limit over-voltages on transistors. One relatively new approach, called Power Chip-on-Chip (PCoC), considers the integration of power dies, one on top of the other, directly in the busbar. This allows for the reduction of the stray inductance. This paper first presents the implementation of a PCoC module using classical packaging techniques. Then a description of the different technological steps for the realization is outlined. Finally, experimental characterization results confirm the lower stray inductances offered by the PCoC package compared with the planar one.

[4+2] thermoreversible Diels-Alder cycloaddition has been used to crosslink star-shaped poly(e-caprolactone) in order to produce networks based on strong carbon-carbon covalent bondings. Depending on the nature of the Diels-Alder reactants, these bonds can be thermoreversibly broken, allowing re-processing of the polymer matrix.

This paper describes the synthesis of a novel amphiphilic AB 2 triarm star-shaped copolymer with A = non-toxic and biocompatible hydrophilic poly(ethylene oxide) (PEO) and B = biodegradable and hydrophobic poly(e-caprolactone) (PCL). A series of AB 2 triarm star-shaped copolymers with different molecular-weights for the PCL block were successfully synthesized by a three-step procedure. α-Methoxy-ω-epoxy-poly(ethylene oxide) (PEO-epoxide) was first synthesized by the nucleophilic substitution of α-methoxy-ω-hydroxy-poly(ethylene oxide) (MPEO) on epichlorohydrin. In a second step, the α-methoxy-ω,ω′-dihydroxy-poly(ethylene oxide) (PEO(OH) 2 ) macroinitiator was prepared by the selective hydrolysis of the ω-epoxy end-group of the PEO-epoxide chain. Finally, PEO(OH) 2 was used as a macroinitiator for the ring-opening polymerization (ROP) of e-caprolactone (eCL) catalyzed by tin octoaote (Sn(Oct) 2 ). PEO-epoxide, PEO(OH) 2 and the AB 2 triarm star-shaped copolymers were assessed by 1 H NMR spectroscopy, size exclusion chromatography (SEC) and MALDI-TOF. The behavior of the AB 2 triarm star-shaped copolymer in aqueous solution was studied by dynamic light scattering (DLS) and transmission electron microscopy (TEM).

International audience; Silver sintering is an attractive alternative to soldering in power electronics, as it offers higher electrical and thermal performance. Furthermore, sintered attaches can operate at a higher temperature. In this paper, we investigate the use of silver sintering for the bonding of passive components, and for the manufacturing of so-called 3D-modules. It is shown that this technique is well suited, as it makes it possible to operate at very high temperature (up to 310 °C demonstrated), and as it simplifies the assembly process (several identical sintering steps can be performed successively without problem).

International audience; The precision synthesis of poly(ionic liquid)s (PILs) in water is achieved for the first time by the cobalt-mediated radical polymerization (CMRP) of N-vinyl-3-alkylimidazolium-type monomers following two distinct protocols. The first involves the CMRP of various 1-vinyl-3-alkylimidazolium bromides conducted in water in the presence of an alkyl cobalt(III) complex acting as a monocomponent initiator and mediating agent. Excellent control over molar mass and dispersity is achieved at 30 degrees C. Polymerizations are complete in a few hours, and PIL chain-end fidelity is demonstrated up to high monomer conversions. The second route uses the commercially available bis(acetylacetonato)cobalt(II) (Co(acac)2) in conjunction with a simple hydroperoxide initiator (tertbutyl hydroperoxide) at 30, 40, and 50 degrees C in water, facilitating the scaling-up of the technology. Both routes prove robust and straightforward, opening new perspectives onto the tailored synthesis of PILs under mild experimental conditions in water.

8 pages; International audience; Although they can operate at elevated junction temperature, silicon carbide power devices can in some cases fail, even at low ambient temperature. This destruction mechanism, called the thermal run-away, is described in the paper. Then, the sensitivity of normally-on SiC JFETs (SiCED) to this mechanism is evaluated using a model based on experimental measurements performed over a wide temperature range (from -50°C to 300°C). It is shown that above a certain current level, run-away can occur. An experimental test bench is used to validate the modelling and explore the safe-operating area of these devices. The measurements confirm the sensitivity of the device to thermal run-away. Mitigation techniques are discussed.

The intraperitoneal biocompatibility of PDMS, polyHEMA and pEVA was investigated in rats, rabbits and rhesus monkeys. No inflammation was evidenced by hematological analyses and measurement of inflammatory markers throughout the experiment and by post-mortem examination of the pelvic cavity. After 3 or 6 months, histological analysis revealed fibrous tissue encapsulating PDMS and PEVA implants in all species and polyHEMA implants in rabbits and monkeys. Calcium deposits were observed inside polyHEMA implants. The intraperitoneal biocompatibility of all 3 polymers makes them suitable for the design of drug delivery systems, which may be of great interest for pathologies confined to the pelvic cavity.

International audience; Le frittage d'argent est un candidat prometteur pour remplacer les brasures haute température au plomb. Il offre en effet de meilleures performances thermiques, électriques, fonctionne à plus haute température. Plusieurs solutions existent actuellement, basée sur des particules d'argent de tailles différentes et l'ajout d'additifs de frittage. Ces solutions diffèrent par leur procédés de mise en oeuvre. Cet article présente un état de l'art des différentes techniques, puis détaille la mise en oeuvre de l'une d'entre elles, basée sur des nanoparticules. Un point particulier est mis en évidence : la finition métallique des substrats DBC. Cette finition a un effet majeur sur la qualité du joint fritté, en particulier avec une finition "Ni-Au" : dans certains cas, l'attache est excellente (tenue upérieure à 50 MPa), alors que dans d'autres, elle est inférieure à 10 MPa.