Hemocompatibility of liposomes loaded with lipophilic prodrugs of methotrexate and melphalan in the lipid bilayer

Natalia R. Kuznetsova, Chantal Sevrin, David Lespineux, Nicolai V. Bovin, Elena L. Vodovozova, T. Mészáros, J. Szebeni, Christian Grandfils

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

A panel of in vitro tests intended for evaluation of the nano-sized drug delivery systems' compliance with human blood was applied to liposomal formulations of anticancer lipophilic prodrugs incorporated into the lipid bilayer. Liposomes on the basis of natural phosphatidylcholine (PC) and phosphatidylinositol (PI), 8:1 (mol) were loaded with 10 mol% of either methotrexate or melphalan 1,2-dioleoylglyceride esters (MTX-DOG and Mlph-DOG respectively) and either decorated with 2 mol% of sialyl Lewis X/A (SiaLe X/A) tetrasaccharide ligand or not. Hemolysis rate, red blood cells and platelets integrity and size distribution, complement (C) activation, and coagulation cascade functioning were analyzed upon the material incubation with whole blood. Both formulations were negatively charged with the zeta potential value being higher in the case of MTX-DOG liposomes, which also were larger than Mlph-DOG liposomes and more prone to aggregation. Accordingly, in hemocompatibility tests Mlph-DOG liposomes did not provoke any undesirable effects, while MTX-DOG liposomes induced significant C activation and abnormal coagulation times in a concentration-dependent manner. Reactivity of the liposome surface was not affected by the presence of SiaLe X/A or PI. Decrease in liposome loading with MTX-DOG from 10 to 2.5% resulted in lower surface charge density, smaller liposome size and considerably reduced impact on C activation and coagulation cascades.

Original languageEnglish
Pages (from-to)394-400
Number of pages7
JournalJournal of Controlled Release
Volume160
Issue number2
DOIs
Publication statusPublished - Jun 10 2012

Fingerprint

Melphalan
Prodrugs
Lipid Bilayers
Methotrexate
Liposomes
Phosphatidylinositols
Complement Activation
Drug Delivery Systems
Hemolysis
Phosphatidylcholines
Esters
Blood Platelets
Erythrocytes
Ligands

Keywords

  • Coagulation tests
  • Complement activation
  • Hemocompatibility
  • Lipophilic prodrugs
  • Liposomes

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Hemocompatibility of liposomes loaded with lipophilic prodrugs of methotrexate and melphalan in the lipid bilayer. / Kuznetsova, Natalia R.; Sevrin, Chantal; Lespineux, David; Bovin, Nicolai V.; Vodovozova, Elena L.; Mészáros, T.; Szebeni, J.; Grandfils, Christian.

In: Journal of Controlled Release, Vol. 160, No. 2, 10.06.2012, p. 394-400.

Research output: Contribution to journalArticle

Kuznetsova, Natalia R. ; Sevrin, Chantal ; Lespineux, David ; Bovin, Nicolai V. ; Vodovozova, Elena L. ; Mészáros, T. ; Szebeni, J. ; Grandfils, Christian. / Hemocompatibility of liposomes loaded with lipophilic prodrugs of methotrexate and melphalan in the lipid bilayer. In: Journal of Controlled Release. 2012 ; Vol. 160, No. 2. pp. 394-400.
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