Complete inhibition of extranodal dissemination of lymphoma by edelfosine-loaded lipid nanoparticles

Abstract

Lipid nanoparticles (LN) made of synthetic lipids Compritol® 888 ATO and Precirol® ATO 5 were developed, presenting an average size of 110.4 ± 2.1 nm and 103.1 ± 2.9 nm, for Compritol® and Precirol®, respectively, and encapsulation efficiency above 85 % for both type of lipids. These LN decrease the hemolytic toxicity of the drug by 90 %. Pharmacokinetic and biodistribution profiles of the drug were studied after intravenous and oral administration of edelfosine-containing LN, providing an increase in relative oral bioavailability of 1500 % after a single oral administration of drug-loaded LN, maintaining edelfosine plasma levels over 7 days in contrast to a single oral administration of edelfosine solution, which presents a relative oral bioavailability of 10 %. Moreover, edelfosine-loaded LN showed a high accumulation of the drug in lymph nodes and resulted in slower tumor growth than the free drug in a murine lymphoma xenograft model, as well as potent extranodal dissemination inhibition.