The effect of lipid composition of small unilamellar liposomes containing melphalan and vincristine on drug clearance after injection into mice.

Melphalan and vincristine together with their radiolabelled derivatives were entrapped in small unilamellar liposomes of varying cholesterol content and phospholipid composition. After intravenous injection of drug-containing egg phosphatidylcholine liposomes into mice, drug clearance rates from the blood were reduced with increasing cholesterol content. Circulating drugs were partially associated with the carrier and partly free, mostly bound to plasma proteins. The ratio of drug associated with liposomes to that circulating as free was dependent on the type of liposomes used and highest when these were cholesterol-rich. Drug clearance rates were reduced and entrapped: free drug ratios increased further when egg phosphatidylcholine in cholesterol-rich liposomes was replaced by sphingomyelin. Drug-containing cholesterol-rich liposomes injected intraperitoneally were found capable of entering the periphery intact and quantitatively to assume clearance rates similar to those observed after intravenous treatment. Such manipulations in liposomal lipid composition can alter pharmacokinetics in ways that could provide optimal conditions for drug distribution into tumours and a therapeutic effect.