A novel approach for the increased delivery of pharmaceutical agents to peritoneum and associated lymph nodes

A novel method for prolonging the retention of liposomes in the peritoneum while increasing liposome deposition in lymph nodes that drain the peritoneum is described. An aliquot (1 ml) of technetium-99m (Tc-99m)-biotin-liposomes encapsulating blue dye was injected intraperitoneally in rats. Thirty minutes after administration of the Tc-99m-blue-biotin-liposomes, five rats (experimental) were administered avidin (5 mg) intraperitoneally, whereas the remaining five rats served as controls. Scintigraphic images were acquired at baseline and 1 and 24 h after the liposome injection followed by a tissue biodistribution study. Images at 24 h clearly demonstrated very different distributions between the experimental and control animals. In experimental rats, most of the activity was visualized in the abdominal region, and in abdominal and mediastinal lymph nodes. The percentage of the injected dose (% ID) in the blood was significantly higher in the control group than in the experimental group (14.0 +/- 1.7 versus 0.17 +/- 0.03%; P < 0.001). The % ID in the spleen was also significantly greater for controls (23.3 +/- 3.9%) compared with the experimental group (0.78 +/- 0.8%; P = 0.001). Significant Tc-99m activity was detected in blue-stained abdominal nodes (4.7%) and mediastinal nodes (2.3%) from the experimental animals, whereas no blue-stained nodes were detectable in the control animals. The intraperitoneal biotin-liposome/avidin delivery system described in this study could potentially be used for delivery of liposome-encapsulated drugs to disease processes that become disseminated in the peritoneum such as metastatic ovarian, gastric, and colorectal cancer, as well as infectious peritonitis.