ARREST OF HUMAN LUNG-TUMOR XENOGRAFT GROWTH IN SEVERE COMBINED IMMUNODEFICIENT MICE USING DOXORUBICIN ENCAPSULATED IN STERICALLY STABILIZEDLIPOSOMES

Incorporation of polyethylene glycol-derivatized phospholipids into li posomes results in carriers that can enhance the therapeutic efficacy of encapsulated drugs by imparting the ability to evade the reticuloen dothelial system and remain in the circulation for prolonged periods. In this study, doxorubicin encapsulated in these sterically stabilized liposomes (S-DOX) is shown to completely arrest the growth of human l ung tumor xenografts in severe combined immunodeficient (scid) mice. D oxorubicin administered at equivalent doses as free drug or encapsulat ed into conventional liposomes was ineffective at completely arresting the growth of this human tumor, although a decrease in tumor growth r ate compared to untreated controls was observed. Scid mice were found to be significantly more susceptible to the toxic effects of doxorubic in than were immunocompetent C.B-17 control mice, a characteristic tha t is likely to result from the deficit in DNA repair mechanisms previo usly identified in scid mice. However, doxorubicin toxicity in scid mi ce could be minimized while maintaining the antitumor activity of doxo rubicin encapsulated in sterically stabilized liposomes by administeri ng the drug in multiple weekly injections at low doses. This report pr ovides the first evidence that antitumor drugs delivered in sterically stabilized liposomes are more effective at arresting the growth of hu man tumors than are conventional delivery systems. In addition, the sc id mouse is presented as a viable model in which to study novel chemot herapeutic approaches to the treatment of human cancer.