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

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...

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Detalles Bibliográficos
Autores: Estella-Hermoso-de-Mendoza, A. (Ander)|||/items/a707a792-b20f-4871-9546-bd9aff90b5c5, Campanero, M.A. (Miguel Angel)|||/items/0023fc84-97ca-4e40-95b4-9fd3c6f755af, Lana, H. (Hugo)|||/items/e924cc6a-f04d-44a0-bc6f-194223a1ecf1, Villa-Pulgarin, J.A. (Janny A.)|||/items/feeed7fa-bf30-4bcb-95fa-e8d7b489e1c1, Iglesia-Vicente, J. (Janis) de la|||/items/a674887e-d357-4425-afb4-30c97b7fc5f3, Mollinedo, F. (Faustino)|||/items/15ff13d8-71ca-4313-a560-a9fb504fc99d, Blanco-Prieto, M.J. (María José)|||/items/93e177db-635f-456f-b672-b79ef8befc40
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/29159
Acceso en línea:https://hdl.handle.net/10171/29159
Access Level:acceso abierto
Palabra clave:Edelfosine
Lipid nanoparticles
Bioavailability
Pharmacokinetics
Biodistribution
Lymphoma
Descripción
Sumario: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.