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

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 Philippe Joly Alexander Scheer Philippe Connes Agnès Cibiel 

机构地区：[1]Erytech Pharma,Lyon 69008,France [2]Laboratoire interuniversitaire de Biologie de la Motricité(LIBM)EA7424,Team«Vascular Biology and Red Blood Cell»,Universite´Claude Bernard Lyon 1,Universite´de Lyon,Lyon 69008,France [3]Labex GR-Ex,Paris 75015,France [4]3P5 proteom’IC facility,Universitéde Paris,Institut Cochin,INSERM,CNRS,Paris 75014,France [5]University of Colorado,Anschutz Medical Campus,Aurora,CO 80045,USA [6]Omix Technologies,Inc.,Aurora,CO 80045,USA [7]Inserm U1016,CNRS 8104,Universitéde Paris,Institut Cochin,Paris 75014,France [8]Laboratoire de Biochimie et de Biologie Moléculaire,UF de biochimie des pathologies e´rythrocytaires,Centre de Biologie et de Pathologie Est,Hospices Civils de Lyon,Bron 69500,France

出　　处：《Acta Pharmaceutica Sinica B》2022年第4期2089-2102,共14页药学学报（英文版）

基　　金：funds from the FEDER through the Operational Programme for Competitiveness Factors and Employment 2007-2013 (France);from the Cancérop?le Ile de France (France)

摘　　要：Red blood cells(RBCs)can act as carriers for therapeutic agents and can substantially improve the safety,pharmacokinetics,and pharmacodynamics of many drugs.Maintaining RBCs integrity and lifespan is important for the efficacy of RBCs as drug carrier.We investigated the impact of drug encapsulation by hypotonic dialysis on RBCs physiology and integrity.Several parameters were compared between processed RBCs loaded with l-asparaginase(“eryaspase”),processed RBCs without drug and non-processed RBCs.Processed RBCs were less hydrated and displayed a reduction of intracellular content.We observed a change in the metabolomic but not in the proteomic profile of processed RBCs.Encapsulation process caused moderate morphological changes and was accompanied by an increase of RBCs-derived Extracellular Vesicles release.Despite a decrease in deformability,processed RBCs were not mechanically retained in a spleen-mimicking device and had increased surface-to-volume ratio and osmotic resistance.Processed 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 forms.Our 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 

分 类 号：R965[医药卫生—药理学]