Nanoscale detection of metal-labeled copolymers in patchy polymersomes

We report the synthesis of polymersome-forming block copolymers using two different synthetic routes based on Atom Transfer Radical Polymerization (ATRP) and Reversible Addition Fragmentation chain Transfer (RAFT) polymerization, respectively. Functionalization with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) allowed the block copolymer chains to be labelled with electron-dense metal ions (e.g. indium). The resulting metal-conjugated copolymers can be visualized by transmission electron microscopy with single chain resolution, hence enabling the study of polymer/polymer immiscibility and phase separation on the nano-scale

Nanogels de polysaccharides pour la délivrance d’insuline

Les nanogels sont de bons candidats pour la délivrance d’actifs. Ces réseaux de polymères réticulés et de taille nanométrique, sont gonflés d’eau. Ils sont donc capables d’encapsuler une protéine à l’intérieur de leurs pores et de la libérer en fonction de l’état de gonflement du réseau. Cet état peut être modulé par la densité de réticulation du réseau ou par l’application d’un stimulus externe tel que le pH, la température ou encore une biomolécule telle que le glucose. Ainsi, les nanogels sensibles au glucose se présentent comme des candidats idéaux pour administrer l’insuline de façon asservie à la glycémie. Afin de satisfaire aux critères de biocompatibilité et de biorésorption des vecteurs, nous avons choisi de développer des nanogels à base de polysaccharide, en particulier à base d’acide hyaluronique (HA). Ceux-ci sont obtenus par réticulation du HA, préalablement modifié par des fonctions réticulables telles que les méthacrylates, dans des nanogouttes d'émulsion eau-dans-huile. Des nanogels de taille et de porosité modulables ont été synthétisés grâce à un bon contrôle 1) de la modification chimique des précurseurs par des fonctions réticulables (taux de méthacrylation), 2) de l’émulsion matricielle (taille, stabilité), 3) des conditions de réticulation par photopolymérisation gouvernant le taux de conversion des méthacrylates. Ce savoir-faire a ensuite été appliqué à la synthèse de nanogels modifiés par des dérivés de l’acide phénylboronique, ligand du glucose, afin d’obtenir des matériaux dont le taux de gonflement varie en fonction de la glycémie. L’intérêt applicatif de ces objets a été évalué vis-à-vis des propriétés d’encapsulation de l’insuline, de dégradabilité enzymatique, et de biocompatibilité.Nanogels are an attractive class of delivery systems. These soft particles, made of highly swollen polymer network, can physically entrap a drug and release it at a rate depending on its diffusion though the network. Therefore, any change in the swelling degree can trigger the release kinetics. This parameter can be tuned by modifying the density of cross-links in the gel matrix or by changing the environmental conditions such as pH, temperature or analyte such as glucose. Thus, glucose-responsive nanogels are good candidates to be used as self-regulated systems for insulin delivery. To fulfill both biocompatibility and biodegradability criteria, our attention has been focused on the design of new nanogels made of polysaccharides, in particular made of hyaluronic acid (HA), as a main constituent. HA was at first covalently modified with polymerizable methacrylate functions and confined in nanoreactors during photopolymerization using water-in-oil miniemulsions as template. Biodegradable nanogels with a well-defined size and various cross-linking degrees were thus achieved, thanks to a good control of 1) the chemical modification of HA with methacrylates (degree of methacrylation) 2) the emulsion template (size, stability), 3) the photopolymerization conditions which governed the conversion rate of the polymerization. Further modification of the polysaccharide with phenylboronic acid as a glucose-sensitive group yielded nanogels whose swelling behavior could vary as a function of glucose concentration. These systems were further studied as insulin delivery systems. Moreover, their biodegradability, stability and biocompatibility were assessed

Nanogels de polysaccharides pour la délivrance d’insuline

Les nanogels sont de bons candidats pour la délivrance d’actifs. Ces réseaux de polymères réticulés et de taille nanométrique, sont gonflés d’eau. Ils sont donc capables d’encapsuler une protéine à l’intérieur de leurs pores et de la libérer en fonction de l’état de gonflement du réseau. Cet état peut être modulé par la densité de réticulation du réseau ou par l’application d’un stimulus externe tel que le pH, la température ou encore une biomolécule telle que le glucose. Ainsi, les nanogels sensibles au glucose se présentent comme des candidats idéaux pour administrer l’insuline de façon asservie à la glycémie. Afin de satisfaire aux critères de biocompatibilité et de biorésorption des vecteurs, nous avons choisi de développer des nanogels à base de polysaccharide, en particulier à base d’acide hyaluronique (HA). Ceux-ci sont obtenus par réticulation du HA, préalablement modifié par des fonctions réticulables telles que les méthacrylates, dans des nanogouttes d'émulsion eau-dans-huile. Des nanogels de taille et de porosité modulables ont été synthétisés grâce à un bon contrôle 1) de la modification chimique des précurseurs par des fonctions réticulables (taux de méthacrylation), 2) de l’émulsion matricielle (taille, stabilité), 3) des conditions de réticulation par photopolymérisation gouvernant le taux de conversion des méthacrylates. Ce savoir-faire a ensuite été appliqué à la synthèse de nanogels modifiés par des dérivés de l’acide phénylboronique, ligand du glucose, afin d’obtenir des matériaux dont le taux de gonflement varie en fonction de la glycémie. L’intérêt applicatif de ces objets a été évalué vis-à-vis des propriétés d’encapsulation de l’insuline, de dégradabilité enzymatique, et de biocompatibilité.Nanogels are an attractive class of delivery systems. These soft particles, made of highly swollen polymer network, can physically entrap a drug and release it at a rate depending on its diffusion though the network. Therefore, any change in the swelling degree can trigger the release kinetics. This parameter can be tuned by modifying the density of cross-links in the gel matrix or by changing the environmental conditions such as pH, temperature or analyte such as glucose. Thus, glucose-responsive nanogels are good candidates to be used as self-regulated systems for insulin delivery. To fulfill both biocompatibility and biodegradability criteria, our attention has been focused on the design of new nanogels made of polysaccharides, in particular made of hyaluronic acid (HA), as a main constituent. HA was at first covalently modified with polymerizable methacrylate functions and confined in nanoreactors during photopolymerization using water-in-oil miniemulsions as template. Biodegradable nanogels with a well-defined size and various cross-linking degrees were thus achieved, thanks to a good control of 1) the chemical modification of HA with methacrylates (degree of methacrylation) 2) the emulsion template (size, stability), 3) the photopolymerization conditions which governed the conversion rate of the polymerization. Further modification of the polysaccharide with phenylboronic acid as a glucose-sensitive group yielded nanogels whose swelling behavior could vary as a function of glucose concentration. These systems were further studied as insulin delivery systems. Moreover, their biodegradability, stability and biocompatibility were assessed

Nanogels de polysaccharides pour la délivrance d'insuline

Les nanogels sont de bons candidats pour la délivrance d actifs. Ces réseaux de polymères réticulés et de taille nanométrique, sont gonflés d eau. Ils sont donc capables d encapsuler une protéine à l intérieur de leurs pores et de la libérer en fonction de l état de gonflement du réseau. Cet état peut être modulé par la densité de réticulation du réseau ou par l application d un stimulus externe tel que le pH, la température ou encore une biomolécule telle que le glucose. Ainsi, les nanogels sensibles au glucose se présentent comme des candidats idéaux pour administrer l insuline de façon asservie à la glycémie. Afin de satisfaire aux critères de biocompatibilité et de biorésorption des vecteurs, nous avons choisi de développer des nanogels à base de polysaccharide, en particulier à base d acide hyaluronique (HA). Ceux-ci sont obtenus par réticulation du HA, préalablement modifié par des fonctions réticulables telles que les méthacrylates, dans des nanogouttes d'émulsion eau-dans-huile. Des nanogels de taille et de porosité modulables ont été synthétisés grâce à un bon contrôle 1) de la modification chimique des précurseurs par des fonctions réticulables (taux de méthacrylation), 2) de l émulsion matricielle (taille, stabilité), 3) des conditions de réticulation par photopolymérisation gouvernant le taux de conversion des méthacrylates. Ce savoir-faire a ensuite été appliqué à la synthèse de nanogels modifiés par des dérivés de l acide phénylboronique, ligand du glucose, afin d obtenir des matériaux dont le taux de gonflement varie en fonction de la glycémie. L intérêt applicatif de ces objets a été évalué vis-à-vis des propriétés d encapsulation de l insuline, de dégradabilité enzymatique, et de biocompatibilité.Nanogels are an attractive class of delivery systems. These soft particles, made of highly swollen polymer network, can physically entrap a drug and release it at a rate depending on its diffusion though the network. Therefore, any change in the swelling degree can trigger the release kinetics. This parameter can be tuned by modifying the density of cross-links in the gel matrix or by changing the environmental conditions such as pH, temperature or analyte such as glucose. Thus, glucose-responsive nanogels are good candidates to be used as self-regulated systems for insulin delivery. To fulfill both biocompatibility and biodegradability criteria, our attention has been focused on the design of new nanogels made of polysaccharides, in particular made of hyaluronic acid (HA), as a main constituent. HA was at first covalently modified with polymerizable methacrylate functions and confined in nanoreactors during photopolymerization using water-in-oil miniemulsions as template. Biodegradable nanogels with a well-defined size and various cross-linking degrees were thus achieved, thanks to a good control of 1) the chemical modification of HA with methacrylates (degree of methacrylation) 2) the emulsion template (size, stability), 3) the photopolymerization conditions which governed the conversion rate of the polymerization. Further modification of the polysaccharide with phenylboronic acid as a glucose-sensitive group yielded nanogels whose swelling behavior could vary as a function of glucose concentration. These systems were further studied as insulin delivery systems. Moreover, their biodegradability, stability and biocompatibility were assessed.BORDEAUX1-Bib.electronique (335229901) / SudocSudocFranceF

Production of controlled and reliable novel stimuli-responsive emulsions for skin care applications with membrane processes

International audienc

Production of controlled and reliable novel nanoemulsions for skin care applications with membrane processes

International audienc

Influence of viscosity for oil-in-water and water-in-oil nanoemulsions production by SPG premix membrane emulsification

International audienceOil-in-water and water-in-oil nanoemulsions are interesting carriers for respectively oil soluble and water soluble actives. In this study, oil-in-water (O/W) and water-in-oil (W/O) nanoemulsions were prepared by premix membrane emulsification. A coarse emulsion (premix) was injected thanks to a high pressure pump through a Shirasu Porous Glass (SPG) membrane with pore size of 0.5 µm in order to reduce and homogenize the droplet size. The effect of viscosities on the pressure and droplet size was investigated: the water phase viscosity by increasing glycerol concentration, the oil phase viscosity with mineral oils of different viscosities and the overall emulsion viscosity by increasing the dispersed phase content of the emulsion. The pressure required to break up the droplets inside the membrane pores ∆P dis did not depend on viscosities, while the pressures generated by the flows through the pipe ∆P pipe and the membrane ∆P f low were proportional to the viscosity of the overall emulsion. W/O nanoemulsions were more difficult to produce and to characterize but thanks to the original setup working at pressures up to 65 bar and high flowrates, W/O mineral oil nanoemulsions were produced with mean droplets size around 600 nm and flow rate of 50 mL/min

Clinical diagnosis, outcomes and treatment of thiamine deficiency in a tertiary hospital

International audienceSummaryBackgroundAcute thiamine deficiency can occur in patients with or without history of alcohol abuse and can lead to life-threatening complications. Clinical diagnosis is challenging, often resulting in delayed recognition and treatment. Patients may present with heterogenous symptoms, more diverse than the historical neurological description. Cerebral MRI can contribute to the diagnosis in patients with neurological signs but it is not always feasible in emergency settings. Prompt parenteral supplementation is required to obtain the improvement of symptoms and avoid chronic complications.AimsTo describe the clinical presentation of reported cases of thiamine deficiency, assess prescription and results of cerebral imaging, review treatments that had been prescribed in accordance or not with available guidelines, and study the short-term outcome of these patients.MethodsThis is a monocentric retrospective analysis of all reported cases of thiamine deficiency in a French tertiary hospital between January 1st 2008 and December 31st 2018.ResultsFifty-six cases were identified during the study period. Forty-five (80%) patients had a history of alcohol abuse. Most patients were diagnosed based on neurological symptoms but non-specific and digestive symptoms were frequent. Thirty-four percent of patients fulfilled clinical criteria for malnutrition. A brain MRI was performed in 54% of patients and was abnormal in 63% of these cases. Eighty-five percent of patients were treated by parenteral thiamine administration and the supplementation was continued orally in 55% of them. The majority of patients initially received 1000 mg daily of IV thiamine but the dose and duration of thiamine supplementation were variable. At the time of discharge, partial or complete improvement of symptoms was noted in 59% of patients.ConclusionThis study highlights the clinical and radiological heterogeneity of thiamine deficiency. These observations should encourage starting thiamine supplementation early in patients with risk factors or suggestive symptoms even in non-alcoholic patients, and underline the importance of early nutritional support

Response to the letter by Onishi and al. regarding “Clinical diagnosis, outcomes and treatment of thiamine deficiency in a tertiary hospital”

International audienceLetter to the Editor Response to the letter by Onishi and al. regarding "Clinical diagnosis, outcomes and treatment of thiamine deficiency in a tertiary hospital" We have read with interest the letter addressed by Onishi and al. about our recent article entitled "Clinical diagnosis, outcomes and treatment of thiamine deficiency in a tertiary hospital". While we agree with the authors' remarks about the diagnosis of thiamine deficiency, we would like to provide some clarifications about the interpretation of our study

Interdisciplinary insights into a 500-year trajectory of an alpine socio-ecological system in Montaimont, France

International audienceThe trajectories of mountain socio-ecosystems are complex and influenced by numerous factors (climate, human practices, slope, etc.). This study combined methods used in palynology, ecology and history to produce complementary data to improve understanding of the trajectories of an alpine socio-ecosystem over the last 500 years. Past changes in vegetation cover and land use were reconstructed along with their impacts on erosion dynamics in Montainmont, a commune in the French Alps. A paleoenvironmental analysis (pollen, coprophilous fungi, sedimentology, geochemistry) was conducted on lake sediment, providing a 500-year record of vegetation and erosion dynamics, and mixed farming history. The historical analysis focused on the reconstruction of the customs and habits of the community of Montaimont through the examination of the historical archives of their administrative district. The historical records provided quantitative data on changes in the forest at the plot scale and qualitative information on landscape management. The ecological approach focused on land use analyses using photo-interpretation of aerial ortho-photographs since the 1950s. This data set was used to conduct a spatially explicit analysis of social-environmental interactions in the past. By combining the three approaches, we were able to document changes in vegetation cover over time as well as changes in forestry and agricultural activities. Our analyses reveal a key tipping point during the past century. The community of Montaimont originally used its landscape for mixed farming activities coupled with intensive exploitation of the forest. During the twentieth century, a major socio-ecological change occurred when crop farming ceased, and forest use decreased. This land abandonment led to spontaneous reforestation. This study demonstrates that an interdisciplinary approach bridges the blind spots inherent to each disciplinary approach, facilitating a better understanding of socio-ecological trajectories