Bukara Katarina, Drvenica Ivana, Ilić Vesna, Stančić Ana, Mišić Danijela, Vasić Borislav, Gajić Radoš, Vučetić Dušan, Kiekens Filip, Bugarski Branko
Department Pharmaceutics, Campus Drie Eiken, University of Antwerp, Antwerp, Belgium; Department of Chemical Engineering, Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia.
Department of Chemical Engineering, Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia.
J Biotechnol. 2016 Dec 20;240:14-22. doi: 10.1016/j.jbiotec.2016.10.017. Epub 2016 Oct 20.
The objective of our study was to develop controlled drug delivery system based on erythrocyte ghosts for amphiphilic compound sodium diclofenac considering the differences between erythrocytes derived from two readily available materials - porcine slaughterhouse and outdated transfusion human blood. Starting erythrocytes, empty erythrocyte ghosts and diclofenac loaded ghosts were compared in terms of the encapsulation efficiency, drug releasing profiles, size distribution, surface charge, conductivity, surface roughness and morphology. The encapsulation of sodium diclofenac was performed by an osmosis based process - gradual hemolysis. During this process sodium diclofenac exerted mild and delayed antihemolytic effect and increased potassium efflux in porcine but not in outdated human erythrocytes. FTIR spectra revealed lack of any membrane lipid disorder and chemical reaction with sodium diclofenac in encapsulated ghosts. Outdated human erythrocyte ghosts with detected nanoscale damages and reduced ability to shrink had encapsulation efficiency of only 8%. On the other hand, porcine erythrocyte ghosts had encapsulation efficiency of 37% and relatively slow drug release rate. More preserved structure and functional properties of porcine erythrocytes related to their superior encapsulation and release performances, define them as more appropriate for the usage in sodium diclofenac encapsulation process.
考虑到来自两种容易获得的材料——猪屠宰场和过期输血人血的红细胞之间的差异,我们研究的目的是开发基于红细胞膜囊泡的两亲性化合物双氯芬酸钠控释给药系统。对起始红细胞、空红细胞膜囊泡和载药膜囊泡在包封效率、药物释放曲线、尺寸分布、表面电荷、电导率、表面粗糙度和形态方面进行了比较。双氯芬酸钠的包封通过基于渗透的过程——逐步溶血来进行。在此过程中,双氯芬酸钠在猪红细胞中发挥温和且延迟的抗溶血作用,并增加钾外流,但在过期人红细胞中则不然。傅里叶变换红外光谱显示,包封的膜囊泡中不存在任何膜脂紊乱,也没有与双氯芬酸钠发生化学反应。检测到存在纳米级损伤且收缩能力降低的过期人红细胞膜囊泡的包封效率仅为8%。另一方面,猪红细胞膜囊泡的包封效率为37%,药物释放速率相对较慢。猪红细胞更完整的结构和功能特性与其优异的包封和释放性能相关,这表明它们更适合用于双氯芬酸钠的包封过程。