title: Fabrication principles and their contribution to the superior in vivo therapeutic efficacy of nano-liposomes remote loaded with glucocorticoids.
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.
authors: Laboratory of Membrane and Liposome Research, Department of Biochemistry, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors: Yuval
authors: Y
authors: Avnir
authors: Keren
authors: K
authors: Turjeman
authors: Deborah
authors: D
authors: Tulchinsky
authors: Alex
authors: A
authors: Sigal
authors: Pablo
authors: P
authors: Kizelsztein
authors: Dina
authors: D
authors: Tzemach
authors: Alberto
authors: A
authors: Gabizon
authors: Yechezkel
authors: Y
authors: Barenholz
mesh_terms: D000818:Animals; D002214:Capsules; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007938:Leukemia / Q000188:drug therapy; D008081:Liposomes; D016399:Lymphoma, T-Cell / Q000188:drug therapy; D008776:Methylprednisolone Hemisuccinate / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy; D018991:Myelin Proteolipid Protein / Q000009:adverse effects; D049329:Nanostructures / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D002214:Capsules; D005938:Glucocorticoids; D008081:Liposomes; D018991:Myelin Proteolipid Protein; D014867:Water; D008776:Methylprednisolone Hemisuccinate