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

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 encapsul...

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Main Authors: Mélanie Robert (Author), Bastien Laperrousaz (Author), Diana Piedrahita (Author), Emilie-Fleur Gautier (Author), Travis Nemkov (Author), Florian Dupuy (Author), Elie Nader (Author), Virginie Salnot (Author), Patrick Mayeux (Author), Angelo D'Alessandro (Author), Catherine Lavazec (Author), Philippe Joly (Author), Alexander Scheer (Author), Philippe Connes (Author), Agnès Cibiel (Author)
Format: Book
Published: Elsevier, 2022-04-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Mélanie Robert  |e author 
700 1 0 |a Bastien Laperrousaz  |e author 
700 1 0 |a Diana Piedrahita  |e author 
700 1 0 |a Emilie-Fleur Gautier  |e author 
700 1 0 |a Travis Nemkov  |e author 
700 1 0 |a Florian Dupuy  |e author 
700 1 0 |a Elie Nader  |e author 
700 1 0 |a Virginie Salnot  |e author 
700 1 0 |a Patrick Mayeux  |e author 
700 1 0 |a Angelo D'Alessandro  |e author 
700 1 0 |a Catherine Lavazec  |e author 
700 1 0 |a Philippe Joly  |e author 
700 1 0 |a Alexander Scheer  |e author 
700 1 0 |a Philippe Connes  |e author 
700 1 0 |a Agnès Cibiel  |e author 
245 0 0 |a Multiparametric characterization of red blood cell physiology after hypotonic dialysis based drug encapsulation process 
260 |b Elsevier,   |c 2022-04-01T00:00:00Z. 
500 |a 2211-3835 
500 |a 10.1016/j.apsb.2021.10.018 
520 |a 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. 
546 |a EN 
690 |a Red blood cells 
690 |a Drug carrier 
690 |a Hypotonic dialysis 
690 |a l-Asparaginase 
690 |a Omics 
690 |a Rheology 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Acta Pharmaceutica Sinica B, Vol 12, Iss 4, Pp 2089-2102 (2022) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S221138352100410X 
787 0 |n https://doaj.org/toc/2211-3835 
856 4 1 |u https://doaj.org/article/a8f68fa014d24b678dc9854433c5e34d  |z Connect to this object online.