| Abstract: | The mouse red blood cell (RBC) and red blood cell ghost (RBCG) have been studied as carriers of methotrexate (MTX). When incubated with high concentrations of MTX, RBCs take up significant quantities of it. However, when active loading techniques, such as the slow dialysis and preswell methods, are applied to those cells, up to 15 times more MTX can be entrapped. We have studied factors critical to the incorporation, leakage, and morphology of RBCGs during their loading with MTX by the slow dialysis and preswell methods. Compounds added to the buffers to maintain the ATP content of the cells and osmolarity play functional roles in this process. The fate of the material entrapped within the ghosts after in vivo administration was shown to be capture by the reticuloendothelial system. The pharmacological efficacy of MTX-loaded RBCGs in treating mice bearing hepatoma ascites tumors was demonstrated by increases in average survival time of 28.5-42.8%. |
