title: Ex vivo encapsulation of dexamethasone sodium phosphate into human autologous erythrocytes using fully automated biomedical equipment.
abstract: Erythrocyte-based drug delivery systems are emerging as potential new solutions for the release of drugs into the bloodstream. The aim of the present work was to assess the performance of a fully automated process (EDS) for the ex-vivo encapsulation of the pro-drug dexamethasone sodium phosphate (DSP) into autologous erythrocytes in compliance with regulatory requirements. The loading method was based on reversible hypotonic hemolysis, which allows the opening of transient pores in the cell membrane to be crossed by DSP. The efficiency of encapsulation and the biochemical and physiological characteristics of the processed erythrocytes were investigated in blood samples from 34 healthy donors. It was found that the processed erythrocytes maintained their fundamental properties and the encapsulation process was reproducible. The EDS under study showed greater loading efficiency and reduced variability compared to previous EDS versions. Notably, these results were confirmed using blood samples from Ataxia Telangiectasia (AT) patients, 9.33±1.40 and 19.41±2.10mg of DSP (mean±SD, n=134) by using 62.5 and 125mg DSP loading quantities, respectively. These results support the use of the new EDS version 3.2.0 to investigate the effect of erythrocyte-delivered dexamethasone in regulatory trials in patients with AT.
authors.affiliation: EryDel SpA, via Sasso 36, 61029, Urbino (PU), Italy. Electronic address: giovanni.mambrini@erydel.com.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mambrini
authors.affiliation: EryDel SpA, via Sasso 36, 61029, Urbino (PU), Italy. Electronic address: marco.mandolini@erydel.com.
authors.forename: Marco
authors.initials: M
authors.lastname: Mandolini
authors.affiliation: EryDel SpA, via Sasso 36, 61029, Urbino (PU), Italy; Department of Biomolecular Sciences, University of Urbino "Carlo Bo", via Saffi 2, 61029, Urbino (PU), Italy. Electronic address: luigia.rossi@uniurb.it.
authors.forename: Luigia
authors.initials: L
authors.lastname: Rossi
authors.affiliation: Department of Biomolecular Sciences, University of Urbino "Carlo Bo", via Saffi 2, 61029, Urbino (PU), Italy. Electronic address: francesca.pierige@uniurb.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pierigè
authors.affiliation: EryDel SpA, via Sasso 36, 61029, Urbino (PU), Italy. Electronic address: giovanni.capogrossi@erydel.com.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Capogrossi
authors.affiliation: EryDel SpA, via Sasso 36, 61029, Urbino (PU), Italy. Electronic address: salvatipatricia@gmail.com.
authors.forename: Patricia
authors.initials: P
authors.lastname: Salvati
authors.affiliation: EryDel SpA, via Sasso 36, 61029, Urbino (PU), Italy. Electronic address: sonja.serafini@erydel.com.
authors.forename: Sonja
authors.initials: S
authors.lastname: Serafini
authors.affiliation: EryDel SpA, via Sasso 36, 61029, Urbino (PU), Italy. Electronic address: luca.benatti@erydel.com.
authors.forename: Luca
authors.initials: L
authors.lastname: Benatti
authors.affiliation: EryDel SpA, via Sasso 36, 61029, Urbino (PU), Italy; Department of Biomolecular Sciences, University of Urbino "Carlo Bo", via Saffi 2, 61029, Urbino (PU), Italy. Electronic address: mauro.magnani@uniurb.it.
authors.forename: Mauro
authors.initials: M
authors.lastname: Magnani
mesh_terms: D019794:2,3-Diphosphoglycerate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001260:Ataxia Telangiectasia / Q000097:blood; D001331:Automation / Q000379:methods*; D016022:Case-Control Studies; D003907:Dexamethasone / Q000031:analogs & derivatives* / Q000097:blood; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods*; D004912:Erythrocytes / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D009997:Osmotic Pressure; D011355:Prodrugs
chemical_list: D006454:Hemoglobins; D011355:Prodrugs; D019794:2,3-Diphosphoglycerate; C004180:dexamethasone 21-phosphate; D019344:Lactic Acid; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D005947:Glucose
keywords: Ataxia telangiectasia; Bioreactors; Carrier erythrocytes; Glucocorticoids; Red cell loader