PLoS ONE (Jan 2011)

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

DOI
https://doi.org/10.1371/journal.pone.0025721
Journal volume & issue
Vol. 6, no. 10
p. e25721

Abstract

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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.