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Complete inhibition of extranodal dissemination of lymphoma by edelfosine-loaded lipid nanoparticles
(Future Medicine, 2012) Campanero, M.A. (Miguel Angel); Mollinedo, F. (Faustino); Blanco-Prieto, M.J. (María José); Estella-Hermoso-de-Mendoza, A. (Ander); Iglesia-Vicente, J. (Janis) de la; Lana, H. (Hugo); Villa-Pulgarin, J.A. (Janny A.)
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.