Mediastinal node and diaphragmatic targeting after intracavitary injection of avidin/99mTc-blue-biotin-liposome system.

A method for delivering drugs to sites of disease extension in mediastinal nodes is described. Mediastinal node and lymphatic distributions were determined after intracavitary injection of the avidin/biotin-liposome system in normal rats. The effect of the injected dose on lymphatic targeting of liposomes after intraperitoneal injection of (99m)Tc-blue-biotin-liposomes and intrapleural injection of avidin, and vice versa, is presented. Scintigraphic imaging was used to follow the movement of (99m)Tc-blue-biotin-liposomes to determine the pharmacokinetics and organ uptake. Tissue biodistribution studies were performed 22 h after injection of the (99m)Tc-blue-biotin-liposomes. Results indicated that independent of the cavity in which each agent was injected, a dose of 5.0 mg of each agent results in higher mediastinal node targeting (8%-10% ID/Organ) as compared with the injection of a 0.5 mg dose (2%-5% ID/Organ, p < 0.05). Targeting of diaphragm and associated lymphatics was observed when (99m)Tc-blue-biotin-liposomes were injected in peritoneum and avidin in pleural space. In contrast, pleural, and pericardial lymphatic targeting was observed when (99m)Tc-blue-biotin-liposomes were injected in pleural space and avidin in peritoneum. Intracavitary injection of the avidin/biotin-liposome system could potentially be used for the delivery of prophylactic drugs that could reduce tumor metastasis and infection spread to mediastinal nodes.

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 ((99m)Tc). 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 (99m)Tc-blue-biotin-liposomes. When avidin was injected before (99m)Tc-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.