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Multiparametric characterization of red blood cell physiology after hypotonic dialysis based drug encapsulation process

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Acta pharmaceutica Sinica B 2022年第4期12卷 2089-2102页

作者： Mélanie Robert Bastien Laperrousaz Diana piedrahita emilie-Fleur Gautier Travis Nemkov Florian Dupuy elie Nader Virginie Salnot patrick Mayeux Angelo D’Alessandro Catherine Lavazec p.ilip.e Joly Alexander Scheer p.ilip.e connes Agnès Cibiel erytech pharma Lyon 69008France Laboratoire interuniversitaire de Biologie de la Motricité(LIBM)eA7424 Team«Vascular Biology and Red Blood Cell»Universite´Claude Bernard Lyon 1Universite´de LyonLyon 69008France Labex GR-ex Paris 75015France 3p5 proteom’IC facility Universitéde ParisInstitut CochinINSERMCNRSParis 75014France University of Colorado Anschutz Medical CampusAuroraCO 80045USA Omix Technologies Inc.AuroraCO 80045USA Inserm U1016 CNRS 8104Universitéde ParisInstitut CochinParis 75014France Laboratoire de Biochimie et de Biologie Moléculaire UF de biochimie des pathologies e´rythrocytairesCentre de Biologie et de Pathologie EstHospices Civils de LyonBron 69500France

Red blood cells(RBCs)can act as carriers for therapeutic agents and can substantially improve the safety,pharmacokinetics,and pharmacodynamics of many *** RBCs integrity and lifespan is important for the efficacy of RBCs as drug *** investigated the impact of drug encapsulation by hypotonic dialysis on RBCs physiology and *** parameters were compared between processed RBCs loaded with l-asparaginase(“eryaspase”),processed RBCs without drug and non-processed *** RBCs were less hydrated and displayed a reduction of intracellular *** observed a change in the metabolomic but not in the proteomic profile of processed *** process caused moderate morphological changes and was accompanied by an increase of RBCs-derived extracellular Vesicles *** a decrease in deformability,processed RBCs were not mechanically retained in a spleen-mimicking device and had increased surface-to-volume ratio and osmotic *** RBCs half-life was not significantly affected in a mouse model and our previous phase 1 clinical study showed that encapsulation of asparaginase in RBCs prolonged its in vivo half-life compared to free *** study demonstrated that encapsulation by hypotonic dialysis may affect certain characteristics of RBCs but does not significantly affect the in vivo longevity of RBCs or their drug carrier function.

关键词： Red blood cells Drug carrier Hypotonic dialysis L-Asparaginase Omics Rheology Morphology Senescence markers

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Does endurance training improve red blood cell aging and hemorheology in moderate-trained healthy individuals?

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Journal of Sport and Health Science 2020年第6期9卷 595-603页

作者： Daniel A.Bizjak Fabian Tomschi Gunnar Bales elie Nader Marc Romana p.ilip.e connes Wilhelm Bloch Marijke Grau Department of Molecular and Cellular Sports Medicine German Sport University CologneCologne 50933Germany Laboratoire LIBM eA7424-equipe“Biologie Vasculaire et du Globule Rouge” UniversitéClaude Bernard Lyon 1Villeurbanne 69100France Laboratoire d’excellence du Globule Rouge GR-ex Paris 75015France Universitédes Antilles InsermUnitéBiologie Intégrée du Globule RougeCHU de PointeàPitrePointe_a PitreGuadeloupe 97157France Institut Universitaire de France Paris 75231France The German Research Centre of elite Sport German Sport University CologneCologne 50933Germany

Objective:To examine the impact of a 6-week endurance training on red blood cell(RBC)aging and deformability of healthy participants to detect possible improved hemorheological and performance-related ***:A total of 31 participants(17 females and 14 males)performed a 6-week moderate training protocol(three 1-h running sessions per week at 70%of maximal heart rate).Blood was sampled before and after the *** from each participant were fractioned according to density and age into 4 RBC *** were examined for changes of RBC properties,including aging distribution,RBC deformability,RBC microparticles,and phosphatidylserine *** and plasma nitrite levels were measured as indicators of nitric oxide ***:Aerobic performance,peak oxygen consumption,ventilatory thresholds,velocity at the aerobic-anaerobic threshold,and lactate at exhaustion improved after *** relative amount of both young RBCs and old RBCs increased,and the amount of the main RBC fraction *** externalization and RBC-derived microparticles *** deformability expressed as shear stress required to achieve half-maximum deformation to theoretical maximal elongation index at infinite shear stress improved in unfractioned RBCs(pe decreased in total(p=0.001),young(ppp=0.020)aged RBCs and in plasma(p=0.002),but not in very old ***:These results indicate that non-endurance-trained healthy participants benefit from a regular moderate running training program because performance-related parameters improve and a younger RBC population with improved RBC properties is induced,which might support oxygen supply in the microcirculation.