Phospholipid Stereospecificity in Liposomal Modulation of Nitrogen Mustard Action

Abstract

Liposomes made of L(α) dipalmitoyl phosphatidyl choline (DPPC) enhance the antitumor efficacy of nitrogen mustard (HN2) in vivo, (Ritter et al, 1981) and in vitro (Ritter et al, 1987). Thus, liposomes act on the tumor cells directly rather than by altering NH2 distribution within the animal. In addition, since HN2 and DPPC liposomes do not associate, liposomes do not physically carry HN2 into tumor cells (Ritter et al, 1987). In lip-osome-treated cells though only slightly more HN2 is taken up, the amounts of cytolytic activity and DNA alkylation are doubled by comparison with HN2-treated controls (Ritter et al, 1987). Thus, liposomes increase the amount of HN2 distributed to the nucleus. By contrast, following Ca-H-treatment there is a 31% increase in cellular HN2 uptake but 50% decrease in DNA alkylation and cytolysis (Ritter et al, 1987). The effects on uptake seem to be much less important than the effects on intracellular distribution.