Effect of Phospholipids on Maintenance of the Cytotoxicity of 1-(2-Chloroethyl)-3- cyclohexyl-1-nitrosourea in Aqueous Suspension

Although the chemotherapeutic agent 1-(2-chloroethyl)-3-cyclohexy 1-1-nitrosourea (CCNU) is highly unstable in aqueous suspension, polar glycerophospholipids, notably phosphatidyl choline, had a protective action on the drug’s cytotoxicity in aqueous suspension. The cytotoxicity of CCNU against C-6 glioma cells in monolayer culture was maintained longer when the drug was preincubated in the presence of phosphatidyl choline (0.5 mg/ml) than when it was preincubated in medium alone or with serum or when other phospholipids were added. Preservation of drug action may have been due to the formation of common micelles between CCNU and the phospholipid. The importance of the lipid interaction to the effectiveness of the nitrosoureas in vivo is unknown, but such interaction could be a factor in the duration of drug action, its access to the central nervous system, and its attachment to cell membranes.