Lymphatic uptake of lipid nanoparticles following endotracheal administration.

A previous publication reported the uptake into the lymphatics of pulmonary administered lipid nanoparticles (LN), after aerosolization and inhalation. In the present study LN clearance from the lungs and lymphatic uptake were further evaluated after endotracheal administration. Nanoparticles prepared with gliceryl behenate were radiolabelled by association to the lipophilic tracer D,L-hexamethylpropylene amine oxime (HMPAO) coupled with 99mTc. Labelling efficiency was 97% and stability in body fluids was demonstrated in vitro. Wistar rats were treated by endotracheal administration and lymphatic uptake was determined upon organ sampling. Endotracheally delivered LN are rapidly eliminated from rat lungs and accumulation in para-aortic, axillary and inguinal lymph nodes starts almost immediately after administration. Translocation of LN across the lung mucosa and their uptake into the lymphatics demonstrate their usefulness as potential drug carriers for lung cancer therapy, as well as for immunization purposes.