THE INCORPORATION OF ESTRAMUSTINE INTO LOW-DENSITY-LIPOPROTEIN AND ITS ACTIVITY IN TISSUE-CULTURE

The incorporation of estramustine into low density lipoprotein (LDL) using a freeze drying technique has been investigated. Complexes of LDL and estramustine containing on average 143 molecules of drug in each LDL particle were produced and the size of the particle increased slightly after drug incorporation. The cytotoxic activity of the complex was measured in vitro against P388 and L-Dan cell lines. The complex was approx. 100-times less active than the free drug in normal media; however, activity increased in media supplemented with lipoprotein-deficient serum. Receptor uptake studies demonstrated that the complex was taken up by the L-Dan cells via the LDL receptor pathway, similar to native LDL. The uptake studies, however, demonstrated that the measured cytotoxic activity was only partly due to uptake via receptors and that non-specific uptake of the complex or drug played a major role. The results indicate that it is possible to incorporate steroidal drugs into LDL and to retain both receptor dependent uptake and cytotoxic activity after drug incorporation, but that highly efficacious drugs may be required to obtain maximal cytotoxic benefit. © 1990.