Complete inhibition of extranodal dissemination of lymphoma by edelfosine-loaded lipid nanoparticles.
BACKGROUND
Lipid nanoparticles (LNs) made of synthetic lipids Compritol(®) 888 ATO and Precirol(®) ATO 5 were developed with an average size of 110.4 ± 2.1 and 103.1 ± 2.9 nm, and an encapsulation efficiency above 85% for both type of lipids. These LNs decrease the hemolytic toxicity of the drug by 90%.


METHODS
Pharmacokinetic and biodistribution profiles of the drug were studied after intravenous and oral administration of edelfosine-containing LNs.


RESULTS
This provided an increase in relative oral bioavailability of 1500% after a single oral administration of drug-loaded LNs, maintaining edelfosine plasma levels over 7 days in contrast to a single oral administration of edelfosine solution, which presented a relative oral bioavailability of 10%. Moreover, edelfosine-loaded LNs 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.
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, E-31008, Spain.
Ander
A
Estella-Hermoso de Mendoza
Miguel A
MA
Campanero
Hugo
H
Lana
Janny A
JA
Villa-Pulgarin
Janis
J
de la Iglesia-Vicente
Faustino
F
Mollinedo
María J
MJ
Blanco-Prieto
D000818:Animals; D004075:Diglycerides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005227:Fatty Acids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D017254:Leukemic Infiltration / Q000188:drug therapy; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D010742:Phospholipid Ethers / Q000737:chemistry
D004075:Diglycerides; D005227:Fatty Acids; D010742:Phospholipid Ethers; C086409:glyceryl behenate; C026659:edelfosine; C009032:precirol