Fabrication principles and their contribution to the superior in vivo therapeutic efficacy of nano-liposomes remote loaded with glucocorticoids

Yuval Avnir, Keren Turjeman, Deborah Tulchinsky, Alex Sigal, Pablo Kizelsztein, Dina Tzemach, Alberto Gabizon, Yechezkel Barenholz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

We report here the design, development and performance of a novel formulation of liposome- encapsulated glucocorticoids (GCs). A highly efficient (>90%) and stable GC encapsulation was obtained based on a transmembrane calcium acetate gradient driving the active accumulation of an amphipathic weak acid GC pro-drug into the intraliposome aqueous compartment, where it forms a GC-calcium precipitate. We demonstrate fabrication principles that derive from the physicochemical properties of the GC and the liposomal lipids, which play a crucial role in GC release rate and kinetics. These principles allow fabrication of formulations that exhibit either a fast, second-order (t 1/2 ~ 1 h), or a slow, zero-order release rate (t 1/2 ~ 50 h) kinetics. A high therapeutic efficacy was found in murine models of experimental autoimmune encephalomyelitis (EAE) and hematological malignancies.

Original languageAmerican English
Article numbere25721
JournalPLoS ONE
Volume6
Issue number10
DOIs
StatePublished - 6 Oct 2011

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