Lymphatic Transport of Liposome-Encapsulated Drugs Following Intraperitoneal Administration – Effect of Lipid Composition

Abstract

Tumor cells often metastasize through lymphatic channels. It follows that localization of antitumor agents in the lymphatics may be therapeutically beneficial. This study determines the extent to which lipid composition controls lymphatic transport of a model compound (¹⁴C-sucrose) in liposomes following intraperitoneal administration in rats. All liposomes tested had mean diameters of approximately 0.2 µm. Liposomes were administerd to thoracic duct cannulated rats, and ¹⁴C was quantified in thoracic lymph, several lymph nodes, blood, urine, and peritoneal wash. Changing liposome composition altered the rate of absorption of ¹⁴C from the peritoneal cavity, stability in biological fluids, and the relative ability of liposomes to be retained by lymph nodes. Stability in biological fluids (plasma and lymph) appeared to be a reasonable predictor of observed lymph node recovery. Direct measures of lymph node level alone were poor measures of the ability of liposomes to function as prototypal lymphatic drug carriers. Neutral liposomes were better at reaching the general circulation following absorption from the peritoneal cavity.