The use of liposomes to study drug-membrane interactions

The effects of free and liposome-encapsulated bleomycin and adriamycin on a human hepatocellular carcinoma cell line were studied in vitro. Free and encapsulated bleomycin inhibited cell growth over 24 hours by the same amount, but DNA synthesis was inhibited more by the encapsulated form. Twenty-five per cent of the cell population showed drug resistance to the free drug, whereas this decreased to 17% with encapsulated bleomycin. These results suggest that the cell membrane plays a role in bleomycin resistance, and that cell death is not solely due to inhibition of DNA synthesis. Encapsulated adriamycin inhibited cell growth and DNA synthesis by the same amount or less than the free drug. Possible explanations are that adriamycin exerts its main cytotoxic action by interacting with the cell surface, or that at the low concentrations used, free drug is taken up more efficiently than the encapsulated drug. Liposomes as drug carriers constitute a useful system for studying the basic mechanisms involved in drug action and in particular the role played by cell membranes.