Kayyali Chair for Pharmaceutical Industry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia ; Department of Biochemistry, College of Pharmacy, Al-Azhar University (Boys), Nasr City, Cairo, Egypt.
Kayyali Chair for Pharmaceutical Industry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Saudi Pharm J. 2014 Jul;22(3):223-30. doi: 10.1016/j.jsps.2013.06.007. Epub 2013 Jan 7.
Paclitaxel (PTX) is formulated in a mixture of Cremophor EL and dehydrated alcohol. The intravenous administration of this formula is associated with a risk of infection and hypersensitivity reactions. The presence of Cremophor EL as a pharmaceutical vehicle contributes to these effects. Therefore, in this study, we used human erythrocytes, instead of Cremophor, as a pharmaceutical vehicle. PTX was loaded into erythrocytes using the preswelling method. Analysis of the obtained data indicates that 148.8 μg of PTX was loaded/mL erythrocytes, with an entrapment efficiency of 46.36% and a cell recovery of 75.94%. Furthermore, we observed a significant increase in the mean cell volume values of the erythrocytes, whereas both the mean cell hemoglobin and the mean cell hemoglobin concentration decreased following the loading of PTX. The turbulence fragility index values for unloaded, sham-loaded and PTX-loaded erythrocytes were 3, 2, and 1 h, respectively. Additionally, the erythrocyte glutathione level decreased after PTX loading, whereas lipid peroxidation and protein oxidation increased. The release of PTX from loaded erythrocytes followed first-order kinetics, and about 81% of the loaded drug was released into the plasma after 48 h. The results of the present study revealed that PTX was loaded successfully into human erythrocytes with acceptable loading parameters and with some oxidative modification to the erythrocytes.
紫杉醇(PTX)是在聚氧乙烯蓖麻油和脱水乙醇的混合物中配制的。这种配方的静脉给药与感染和过敏反应的风险有关。聚氧乙烯蓖麻油作为药物载体的存在促成了这些影响。因此,在这项研究中,我们用人红细胞代替聚氧乙烯蓖麻油作为药物载体。使用预溶胀法将 PTX 载入红细胞。对获得的数据的分析表明,148.8μg 的 PTX 载入/mL 红细胞,包封效率为 46.36%,细胞回收率为 75.94%。此外,我们观察到红细胞平均细胞体积值显著增加,而载药后平均细胞血红蛋白和平均细胞血红蛋白浓度均降低。未载入、假载入和载入 PTX 的红细胞的湍流脆性指数值分别为 3、2 和 1 小时。此外,载药后红细胞谷胱甘肽水平下降,而脂质过氧化和蛋白质氧化增加。载药红细胞中 PTX 的释放遵循一级动力学,48 小时后约 81%的载药药物释放到血浆中。本研究的结果表明,PTX 成功地载入人红细胞,具有可接受的载药参数,并对红细胞产生了一些氧化修饰。