The accumulation by fibroblasts of liposomally encapsulated vinblastine

Abstract

Vinblastine, an anti-mitotic agent, was entrapped in liposomes prepared from phosphatidylcholine, cholesterol and stearylamine (mole ratio 7:2:1), and such liposomes incubated with cultured rat embryo fibroblasts. The fibroblasts accumulated the liposomally encapsulated vinblastine in a markedly different manner to that observed for the free agent. In the former case there was an initial high rate of drug uptake followed by a linear accumulation, which was parallel to that of a liposomal membrane marker and although the ratio of accumulated vinblastine to lipid was different to that pertaining to the original preparation prior to incubation, the ratio did remain constant over the linear phase of accumulation. The effect upon the accumulation of incubation temperature and of release experiments indicated that the mechanism of uptake of a liposomally encapsulated drug by fibroblasts was complex, possibly involving a combination of adsorption and endocytosis.