Avidin/biotin-liposome system injected in the pleural space for drug delivery to mediastinal lymph nodes

The objective of this study was to develop a more effective liposome-based method for delivering drugs to mediastinal nodes. Nodal uptake was determined after intrapleural injection of the avidin/biotin-liposome system in normal rats. The effect of injection sequence (avidin injected 2 h before biotin-liposomes and vice versa), volume injected, and administered dose of the agents is described. Pharmacokinetics of the avidin/biotin-liposome system was monitored with scintigraphic imaging by labeling the biotin-liposomes with technetium-99m (Tc-99m). To identify the nodes during the biodistribution studies, patent blue dye was encapsulated in the biotin-liposomes. Tissue biodistribution studies were performed 22 h after injection of the Tc-99m-blue-biotin-liposomes. When avidin was injected before Tc-99m-blue-biotin-liposomes, better mediastinal node targeting (15.7%; p < 0.05) was achieved than when biotin-liposomes were injected first (8.3%) or when only biotin-liposomes were injected (1.0%). Injection of a small dose of liposomes (0.5 mg phospholipid) and avidin (0.5 mg) resulted in the most favorable drug delivery to mediastinal nodes and other organs. Intrapleural injection of the avidin/biotin-liposome system could potentially be used for drug delivery to disease processes such as lung cancer, anthrax, and tuberculosis that invade mediastinal nodes and use them as centers of incubation and dissemination. (C) 2004 Wiley-Liss, Inc.