INCORPORATION OF PREDNIMUSTINE INTO LOW-DENSITY-LIPOPROTEIN - ACTIVITY AGAINST P388 CELLS IN TISSUE-CULTURE

The steroidal anticancer drug prednimustine has been incorporated into low density lipoprotein (LDL) using a lyophilisation technique. The resulting complexes contained 163 mol prednimustine/mol LDL, but were approx. 4 times larger than the native lipoprotein. The complexes retained a degree of in vitro cytotoxic activity against P388 leukaemia cells but this was 10 times less than that of the free drug. The complex was internalised by P388 cells via the LDL receptor pathway with a similar affinity for the receptor but a lower uptake and number of receptors per cell. The results demonstrate that the cytotoxicity of the particular complex is not mediated through the LDL receptor pathway and that other drug uptake mechanisms must be operative in vitro.