Increased stimulation of alkaline phosphatase by small doses of colchicine entrapped in liposomes. A biochemical test to detect effective liposome-hepatocyte interaction.

The subcutaneous administration of colchicine encapsulated in small unilamellar vesicles reduced the initial toxicity peak and maintained for several days an adequate level of the drug in the liver. Colchicine is an excellent marker for effective liposome-hepatocyte interaction since it fulfills the following criteria: (a) When taken up by the hepatocytes within liposomes, it is active and induces the synthesis of alkaline-phosphatase two to three times over control values. The injection of at least ten times more free colchicine is necessary to attain a similar induction. (b) If released from extracellular liposomes, colchicine is cleared rapidly from the circulation. The results show that liposomes, in spite of their reduced aqueous compartment (approximately 1.0 microliter/mumole of lipid), can achieve clinical utility when administered subcutaneously because of their efficient interaction with parenchymal cells and their continual arrival from the injection site.