ATP-loaded liposomes for treatment of myocardial ischemia.
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.
Hartner
William C
WC
Departmentof Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Verma
Daya D
DD
Levchenko
Tatyana S
TS
Bernstein
Eugene A
EA
Torchilin
Vladimir P
VP
D000255:Adenosine Triphosphate / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D017202:Myocardial Ischemia / Q000188:drug therapy*
D008081:Liposomes; D000255:Adenosine Triphosphate