RETRATO SIN IDENTIFICAR [Material gráfico]

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte, 201

Echogenicity enhancement by end-fluorinated polylactide perfluorohexane nanocapsules: Towards ultrasound-activable nanosystems

International audienc

Pyrazinoic acid-Poly(malic acid) biodegradable nanoconjugate for efficient intracellular delivery

International audienc

Lymphatic Transport and Lymph Node Location of Microspheres Subcutaneously Injected in the Vicinity of Tumors in a Rabbit Model of Breast Cancer

International audienc

Biodegradable Pickering emulsions of Lipiodol for liver trans-arterial chemo-embolization

International audienceWater-in-oil (W/O) Lipiodol emulsions remain the preferable choice for local delivery of chemotherapy in the treatment of hepatocellular carcinoma. However, their low stability severely hampers their efficiency. Here, remarkably stable W/O Lipiodol emulsion stabilized by biodegradable particles was developed thanks to Pickering technology. The addition of poly(lactide-co-glycolide) nanoparticles (NPs) into the aqueous-phase of the formulation led to W/O Pickering emulsion by a simple emulsification process through two connected syringes. Influence of nanoparticles concentration and water/oil ratio on emulsion stability and droplet size were studied. All formulated Pickering emulsions were W/O type, stable for at least one month and water droplets size could be tuned by controlling nanoparticle concentration from 24 mm at 25 mg/mL to 69 mm at 5 mg/mL. The potential of these emulsions to efficiently encapsulate chemotherapy was studied through the internalization of doxorubicin (DOX) into the aqueous phase with a water/oil ratio of 1/3 as recommended by the medical community. Loaded-doxorubicin was released from conventional emulsion within a few hours whereas doxorubicin from stable Pickering emulsion took up to 10 days to be completely released. In addition, in vitro cell viability evaluations performed on the components of the emulsion and the Pickering emulsion have shown no significant toxicity up to relatively high concentrations of NPs (3 mg/mL) on two different cell lines: HUVEC and HepG2. Statement of Significance We present an original experimental research in the field of nanotechnology for biomedical applications. In particular, we have formulated, thanks to Pickering technology, a new therapeutic emulsion stabilized with biodegradable PLGA nanoparticles. As far as we know, this is the first therapeutic Pickering emulsion reported in the literature for hepatocellular carcinoma. Such a new emulsion allows to easily prepare a predictable and stable lipiodolized emulsion having all the required characteristics for optimum tumor uptake. As demonstrated throughout our manuscript, emulsions stabilized with these nanoparticles have the advantage of being biodegradable, biocompatible and less toxic compared to usual emulsions stabilized with synthetic surfactants. These findings demonstrate the plausibility of the use of Pickering emulsions for chemoembolization as a therapeutic agent in extended release formulations

Pickering-Emulsion for Liver Trans-Arterial Chemo-Embolization with Oxaliplatin

International audienc

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Les nouveaux biomatériaux de l’embolisation

La disparition du corps étranger, la possibilité d’emboliser à nouveau, la délivrance totale du médicament en un temps donné font tout l’intérêt des emboles dégradables. La réalisation de tels emboles est délicate car il faut respecter un cahier des charges contraignant (mise en suspension dans des solutions physiologiques et des produits de contraste radiologique, injection dans des cathéters), tout en garantissant une dégradation en un temps donné et la possibilité d’un chargement en chimiothérapie. Les travaux réalisés ces dernières années ont exploré diverses voies et produit des résultats suffisamment intéressants pour qu’on puisse affirmer que la révolution du dégradable a commencé en embolisation

Synthèse et formulation des nanoparticules polymère ciblant l'E-sélectine (évaluation in vitro dans un modèle d'endothélium activé.)

Ce travail de thèse avait pour objectif d élaborer un système vecteur ciblantl endothélium pathologiquement activé dans les tissus enflammés, infectés ou tumoraux.Ce vecteur est sous forme de nanoparticules décorées de ligands glycosides capablesd interagir avec l E-sélectine, un récepteur exprimé sur les cellules endothélialesactivées.Nous avons mis au point une synthèse de copolymère amphiphile avec une architectureà bloc muni sur sa partie hydrophile d un ligand glucidique. Ce copolymère a été par lasuite utilisé pour la préparation de nanoparticules de type coeur/couronne. La partiehydrophobe centrale est entourée d une couronne hydrophile dont l'encombrementstérique et la mobilité limitent l'opsonisation de la particule. Le ciblage actif a été assurépar la présence d un ligand du récepteur de l E-sélectine aux extrémités des chaînes depolymères hydrophiles à la surface du vecteur.Avec ces nanoparticules dont les propriétés de surface sont prédéfinies, nous avonsmontré in vitro l association efficace avec les cellules endothéliales activées, ce qui apermis de valider ce concept de ciblage moléculaire actif par l intermédiaire du couplerécepteur/ ligand. Un tel système permettra d améliorer l indice thérapeutique et labiodistribution des principes actifs anti-inflammatoire et/ou anticancéreux.The objective of this work was to develop a delivery system targeting pathologically activated endothelium within inflamed, infectious, and some tumoral tissues. This system is composed of nanoparticles bearing sugar residues that are able to recognize and interact with E-selectin, a receptor expressed on the activated endothelial cells.We synthesized an amphiphilic block copolymer with the hydrophilic part terminated by a carbohydrate ligand. The construction was achieved by a combination of click chemisty, ring-opening polymerization and atom transfer radical polymerization. This copolymer was used to prepare nanoparticles of the core/shell type where the central hydrophobic body is surrounded with the hydrophilic shell that can stabilize the particles in aqueous media and limit their opsonisation. Active targeting was achieved by coupling an analogue of sialyl Lewis X, the physiological ligand of E-selectin to the end of the hydrophilic polymer chains on the surface of the particles.We were able to demonstrate in vitro the efficient association of these nanoparticles with defined surface properties with activated endothelial cells. This allowed us to validate our concept of active molecular targeting using this couple receptor/ligand couple. Such a system could be used to improve the therapeutically index and the biodistribution of anti-inflammatory and anti-tumor drugs.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF