The effect of liposome (phospholipid vesicle) entrapment of actinomycin D and methotrexate on the in vivo treatment of sensitive and resistant solid murine tumours

Abstract

When tested in mice bearing the Ridgway osteosarcoma (ROS) the activity of methotrexate entrapped in small cationic liposomes was increased, both in terms of tumour growth inhibition and toxicity for normal tissues. Conversely, actinomycin D entrapped in small cationic liposomes lost its cytotoxic activity, both against the tumor and normal tissues. In addition, liposome-entrapped actinomycin D proved ineffective therapeutically against a new ROS tumour subline in which resistance to free drug had been derived in vivo; moreover, this resistance appeared to have resulted from failure to retain drug rather than through impaired drug uptake. These results, and those obtained from tissue distribution studies using free and liposome-entrapped actinomycin D, suggested that (a) liposome entrapment modifies the pharmacokinetics and hence activity of these drugs by acting as a slow release system rather than by providing a means of selective delivery to tumours, and (b) the use of liposome-entrapped actinomycin D to overcome drug resistance acquired in vivo may be inappropriate.