LYMPHATIC ABSORPTION AND TISSUE DISPOSITION OF LIPOSOME-ENTRAPPED [ADRIAMYCIN-C-14 FOLLOWING INTRAPERITONEAL ADMINISTRATION TO RATS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (4) , 1311-1317
Abstract
The lymphatic absorption and tissue distribution of free [14C]adriamycin, empty [3H]liposomes, free [14C]adriamycin plus empty [3H]liposomes and [14C]adriamycin entrapped into [3H]liposomes were examined at intervals after i.p. injection into rats. Following treatment with empty [3H]liposomes, almost 30% of the liposomal lipid marker was recovered in 24 h thoracic duct lymph; when [14C]adriamycin was added to or encapsulated in liposomes, this value was reduced to 10%. Only 1% of free [14C]adriamycin was recovered in 24 h lymph; liposomal encapsulation produced a 6-fold increase in this value. Studies on the tissue distribution of the liposomal lipid marker after dosing with empty liposomes revealed uptake by diaphragm, liver and spleen; the highest tissue concentrations were noted in lymph nodes. Liposomal encapsulation of adriamycin altered its tissue disposition, chiefly by increasing the concentration of drug equivalents in diaphragm, liver and spleen. Although free adriamycin was accumulated by lymph nodes to some extent, this lymph node accumulation was markedly enhanced by liposomal encapsulation and was present only in those nodes through which lymph draining the peritoneal cavity passes. This finding and the observation that diaphragm and thoracic duct lymph contain relatively high levels of liposomal lipid and adriamycin equivalents indicate that liposomes are selectively absorbed from the peritoneal cavity by lymphatics and are retained by certain lymph nodes. I.p. administration of liposome-encapsulated drugs may provide a means of selectively concentrating antitumor agents in lymphatic channels and lymph nodes.