Engineering erythrocytes as a novel carrier for the targeted delivery of the anticancer drug paclitaxel

摘要

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@mg 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 1h, 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 48h. 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.