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WIREs Nanomed Nanobiotechnol
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ATP‐loaded liposomes for treatment of myocardial ischemia

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Abstract A major obstacle to drug therapy for treatment of potential myocardial infarction is the limited access to the ischemic myocardium by drugs in an active form. Encouraging results have been reported with liposomes loaded with ATP in a variety of in vitro and in vivo models. We describe methods for optimized encapsulation of ATP in liposomes, enhancement of their effectiveness by increasing circulation time, and targeting of injured myocardial cells with surface attached antimyosin. In isolated ischemic rat hearts, ATP‐loaded liposomes and ATP‐loaded immunoliposomes effectively protected myocardium from ischemia/reperfusion damage as measured by systolic and diastolic functional improvements. In vivo, in rabbits with induced localized myocardial ischemia, liposomal encapsulation of ATP significantly diminished the proportion of ventricular muscle at risk that was irreversibly damaged during reperfusion. Therefore, ATP encapsulated in liposomes can provide an effective exogenous source for in vivo application which can protect ischemically damaged hearts. Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease

Protective effect of liposomes loaded with ATP(ATP‐L) infusion on left ventricular developed pressure (LVDP) (A) and left ventricular end diastolic pressure (LVEDP) (B) after global ischemia and reperfusion in isolated rat heart (mean±SE), n=7–10.

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Scatterplot showing the relationship between the weight of the ischemic left ventricle at risk and the infarcted weight of the ventricle at risk in liposomes loaded with ATP (ATP‐L)‐treated and in the combined empty liposomes + Krebs‐Henseleit (EL + KH) buffer‐treated rabbits.54.

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Protective effect of ATP‐IL, IL, and liposomes loaded with ATP (ATP‐L) infusion on left ventricular developed pressure (LVDP) (A), left ventricular end diastolic pressure (LVEDP) (B) after global ischemia and reperfusion in isolated rat heart (mean ± SE), n=6–11.

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ELISA results with the myosin monolayer for the native 2G4 anti‐myosin antibody (; 2G4‐poly(ethyleneglycol)‐phosphatidylethanol‐amine (PEG‐PE) conjugate (•); 2G4‐PEG‐PE‐bearing ATP‐containing PEG‐liposomes (▴); and 2G4‐free ATP‐containing PEG‐liposomes (▪).

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Microscopy of 7µ M thick heart cryosections fixed with 4% formaldehyde, washed with PBS, and mounted with Fluor mounting media (Trevigen). (a) Extensive association of rhodamine‐phosphatidyl‐ethanol‐amine (Rh‐PE) and fluorescein‐isothiocyanate (FITC) fluorescence with ischemic tissue; (b) Lack of fluorescence associated with normal tissue. (1) Transmission microscopy; (2) Fluorescence microscopy with FITC filter; (3) Fluorescence microscopy with rhodamine (Rh) filter; 4 —Superposition of (2) and (3).

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Protective effect of liposomes loaded with ATP (ATP‐L) (Incubated with ATPase for 60 min at 370C prior to infusion) on left ventricular developed pressure (LVDP) (a) and left ventricular end diastolic pressure (LVEDP) (b) after global ischemia and reperfusion in isolated rat heart (mean ± SE), n=4.

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Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease

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