Hemin formulated in hyaluronan liposomes for treating inflammatory diseases

THE NEED
Myocardial infarction (MI) (ie, heart attack) is the irreversible necrosis of heart muscle secondary to prolonged ischemia. Approximately 1.5 million cases of MI occur annually in the United States.
One of the major challenges in modern cardiology is to optimize myocardial healing and repair. After MI, the heart tries to compensate itself by left ventricular remodeling. One of the earliest phases after MI involves acute inflammation leading to fibrosis and scar formation. Neutrophils and monocytes are the first to infiltrate the infarct. Monocytes become macrophages, which then take part in the acute inflammation as well as in the following phases.
Uncontrolled activation of pro-inflammatory macrophages after myocardial infarction (MI) accelerates adverse left ventricular (LV) remodeling and dysfunction.
TECHNOLOGY
The technology offered here is a method to direct macrophages into healing and reparative activity which could improve myocardial protection, infarct healing and repair. This technology is based on targeting macrophages with liposomes (HA-LP) loaded with hemin.
Hemin, an iron-containing porphyrin, activates heme oxygenase-1 (HO-1), an enzyme with anti-inflammatory and cytoprotective properties, and suppress HIF-alfa with pro-inflammatory properties.
Preliminary experiments of this technology in mouse model of MI, shows that injection of hemin/HA-L promotes the production of an alternative repartive macrophages that produce therapeutic cytokines. The liposomes can be delivered by intravenous (IV), intracoronary (IC) or intramuscular (IM) injection. The experiments readout shows that during acute MI in mouse, IV injection hemin/HA-L switches the phenotype of macrophages from a pro-inflammatory to a reparative phenotype. Therefore hemin could provide a beneficial therapeutic effect for improving infarct healing or reducing macrophage-mediated inflammation in other diseases such as the vessel wall during atherosclerosis.

Hemin/HA-liposomes enhance myocardial healing and repair after myocardial infarction.
POTENTIAL APPLICATION
• Treatment of post of myocardial infraction event.
• Platform treatment of inflammatory diseases such as myocarditis, atherosclerosis and any other inflammatory disease.
ADVANTAGES
• Recruiting self's factors (macrophages) to minimize the inflammation effect to prevent remodeling and rehearsal of heart attack and to repair and recover the myocardial tissue.
• Using targeted delivery agents such as liposome with hyaluronan bound covalently is much more effective formulation to administer drug as it will aim exactly to macrophage membrane.
• Using hemin proved to switch the phenotype of macrophages from a pro-inflammatory to a reparative phenotype.
• Using the technology of liposome engulfed drug (hemin) enables delivering it by intravenous (IV), intracoronary (IC) or intramuscular (IM) injection.
PATENTS
• Title of patent application: IRON OXIDE NANOPARTICLES FOR USE IN TREATING NON-INFECTIOUS INFLAMMATORY DISORDERS
• PCT/IL2011/000300
• National Phase in US EU and IL

Project manager

Elisha Natan
Director BD

Project researchers

Rimona Margalit
T.A.U Tel Aviv University, Life Sciences
The Department of Biochemistry and Molecular Biology

Jonathan Leor
T.A.U Tel Aviv University, Medicine-Sackler Faculty
Neufeld Cardiac Res Inst.-Sheba