Prevention of toxicity to isolated hepatocytes by liposome entrapment of chenodeoxycholic acid.

Cellular uptake and cytotoxicity of chenodeoxycholic acid, delivered free or encapsulated in liposomes, were compared in isolated rat hepatocytes. As quantified by leakage of cytoplasmic and lysosomal enzymes into the medium, cells exposed to free chenodeoxycholic acid displayed a dose-dependent cytotoxic response. Cellular uptake of the drug was either similar or less for free than for entrapped chenodeoxycholic acid at 100 to 400 microM. However, the cytolytic changes were prevented when the cells were exposed to liposome-encapsulated drug. The prevention of cytotoxicity by delivering the drug entrapped in liposomes indicates that the free drug has the capacity to injure cell membranes directly, and suggests that drug-membrane interactions play a role in the hepatotoxic potential of chenodeoxycholic acid.