Ex vivo encapsulation of dexamethasone sodium phosphate into human autologous erythrocytes using fully automated biomedical equipment

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• 作者：Giovanni Mambrini^a ; ^{giovanni.mambrini@erydel.com} ; Marco Mandolini^a ; ^{marco.mandolini@erydel.com} ; Luigia Rossi^a ; ^b ; ^{luigia.rossi@uniurb.it} ; Francesca Pierigè ; ^b ; ^{francesca.pierige@uniurb.it} ; Giovanni Capogrossi^a ; ^{giovanni.capogrossi@erydel.com} ; Patricia Salvati^a ; ^{salvatipatricia@gmail.com} ; Sonja Serafini^a ; ^{sonja.serafini@erydel.com} ; Luca Benatti^a ; ^{luca.benatti@erydel.com} ; Mauro Magnani^a ; ^b ; ^{mauro.magnani@uniurb.it}
• 关键词：AT ; ataxia telangiectasia ; DSP ; dexamethasone sodium phosphate ; EDS ; EryDex system ; EDS-EP ; EDS end product ; GLP ; good laboratory practice ; GMP ; good manufacturing practice ; HCT ; hematocrit ; HD ; healthy donor ; HGB ; hemoglobin ; HPLC ; high-performance liquid chromatography ; HV ; healthy volunteer ; LLOQ ; lower limit of quantification ; MCH ; mean cellular hemoglobin ; MCHC ; mean cellular hemoglobin concentration ; MCV ; mean cellular volume ; MDD ; Medical Device Directive ; PhEur ; European Pharmacopoeia ; P
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：30 January 2017
• 年：2017
• 卷：517
• 期：1-2
• 页码：175-184
• 全文大小：1240 K
• 卷排序：517

文摘

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 ± 2.10 mg of DSP (mean ± SD, n = 134) by using 62.5 and 125 mg 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.