Growth inhibitory effects of liposome‐associated 1‐ O ‐octadecyl‐2‐ O ‐methyl‐ sn ‐glycero‐3‐phosphocholine

The growth inhibitory effects of 1‐ O ‐octadecyl‐2‐ O ‐methyl‐ sn ‐glycero‐3‐phosphocholine (ET‐18‐OCH 3 ) and various liposome compositions of ET‐18‐OCH 3 were compared in a standardized growth inhibition assay utilizing a diverse tumor cell line panel including cell lines expressing multidrug resistance. ET‐18‐OCH 3 and ELL‐12 (4∶3∶1∶2, dioleoylphosphatidylcholine/cholesterol/dioleoylphosphatidylethanolamine‐glutaric acid/ET‐18‐OCH 3 ), an optimal liposomal ET‐18‐OCH 3 formulation, inhibited growth in the micromolar range in drug‐sensitive and‐resistant cells. In general, ET‐18‐OCH 3 ‐liposomes were about twofold less growth inhibitory than ET‐18‐OCH 3 . However, the known hemolytic effects of ET‐18‐OCH 3 were greatly reduced, up to 20 or more times, by liposome association. The effects of ET‐18‐OCH 3 and ELL‐12 were compared in intracellular [Ca 2+ ] modulation and DNA fragmentation assays. ET‐18‐OCH 3 elicited both concentration‐ and serum‐dependent transient and permanent increases in intracellular [Ca 2+ ]. In contrast, ELL‐12 did not modulate intracellular [Ca 2+ ]. ET‐18‐OCH 3 and ELL‐12 similarly affected DNA fragmentation, which may be indicative of apoptosis. The results suggest that, although the specific growth inhibitory effects of ET‐18‐OCH 3 and ELL‐12 are similar, associating ET‐18‐OCH 3 with stable well‐characterized liposomes eliminates nonspecific cell membrane‐associated lytic effects.