Targeting colloidal particulates to thoracic lymph nodes

Background: Thoracic lymphatics and lymph nodes can be affected by cancer and other diseases. Micro- or nanoparticulates are used as carriers for therapeutic agents. We investigated the Lymphatic distribution after intrapleural administration of three different particulates. Methods: Various micro- and nanoparticles of charcoal, polystyrene and poly(lactide-co-glycolide) were administered into the pleural space of rats to study the lymphatic distribution of particles from the pleural cavity to the thoracic lymph nodes. Experimental animal models included healthy rats, rats following pneumonectomy and rats bearing orthotopic lung cancer to mimic relevant clinical scenarios and pathophysiology. Macroscopic examination, tight microscopy, fluorescence microscopy complemented by transmission electron microscopy analysis of the lymphatic tissue allowed precise mapping and detection of the particulates in the thoracic lymphatic system. Results: We found that (1) the particles studied are cleared by the regional thoracic lymphatic system when placed in the pleural space; (2) the lymphatic uptake occurred as early as 3 h after injection and is primarily through the parietal pleura; (3) the transport of particles to regional lymph nodes was consistently found in all three animal models; (4) particles of 0.7-2 mu m in size give the best lymphatic distribution. Conclusions: Regional thoracic lmphatics and lymph nodes can be accessed by collidal particles injected into the pleural space. (c) 2005 Elsevier Ireland Ltd. All rights reserved.