Targeted Delivery of Cardioprotective Drugs

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43HL105167-01
Agency Tracking Number: HL105167
Amount: $385,462.00
Phase: Phase I
Program: SBIR
Awards Year: 2010
Solicitation Year: 2010
Solicitation Topic Code: NHLBI
Solicitation Number: PHS2010-2
Small Business Information
SIBTECH, INC.
115A Commerce Drive, Brookfield, CT, 06804
DUNS: 966566465
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 MARINA BACKER
 (203) 775-5668
 MBACKER@SIBTECH.COM
Business Contact
 BACKER JOSEPH
Phone: (203) 775-5677
Email: jbacker@sibtech.com
Research Institution
N/A
Abstract
DESCRIPTION (provided by applicant): Myocardial infarction is a disabling disease, with infarct size being a major determinant of mortality. To limit infarct size and improve functional recovery, the ischemic myocardium has to be reperfused. However, reperfusion itself causes irreversible damage to the previously ischemic myocardium. A significant part of cardiac injury is caused by apoptosis that starts immediately at the beginning of reperfusion. Therefore, reperfusion injury is considered an important new pharmacologic target for the treatment of patients with ongoing acute myocardial infarction. We propose to develop a targeted liposomal formulation of two drugs proven to protect myocardium through independent mechanisms. Drug-carrying liposomes will be decorated with human annexin V for targeting to phosphatidylserine exposed on the surface of cardiomyocytes at the early stages of apoptosis. Intravenous administration of such liposomes immediately before the beginning of reperfusion could serve as an adjunct therapy for angioplasty and/or thrombolytic administration, which are the standard of care for patients with myocardial infarction. The advantages of the proposed strategy are: 1) delivery of pharmacologically significant amounts of drugs in cardiomyocytes from the first moments of reperfusion, when apoptosis is still reversible, 2) avoiding adverse effects of high-dose regimens that are necessary for free drugs, and 3) intracellular delivery of two drugs working via independent mechanisms increases the probability of successful treatment. Targeted drug-loaded liposomes will be evaluated in primary cultures of cardiomyocytes. We will establish mechanism(s) of internalization in early apoptotic cells and evaluate the therapeutic potential of annexin-targeted drug-loaded liposomes. Biodistribution, targeted drug delivery and the protective effects of the liposomes in vivo will be studied in a mouse model of myocardial ischemia/reperfusion. If successful, the proposed strategy will establish the feasibility of using annexin- targeted therapeutic liposomes as an adjunct therapy for myocardial infarction. It will also advance new technologies in developing therapeutic liposomes for targeted delivery to early-stage apoptotic cells. PUBLIC HEALTH RELEVANCE: We propose to test feasibility of developing a targeted liposomal formulation for two drugs proven to protect ischemic myocardium from lethal reperfusion injury through independent mechanisms. Drug-carrying liposomes will be decorated with human annexin V for targeting to phosphatidylserine exposed on the surface of cardiomyocites at the early stages of apoptosis. Intravenous administration of such liposomes immediately before the beginning of reperfusion could serve as an adjunct therapy for angioplasty and/or thrombolytic administration, which are the standard of care for patients with acute myocardial infarction.

* information listed above is at the time of submission.

Agency Micro-sites

SBA logo
Department of Agriculture logo
Department of Commerce logo
Department of Defense logo
Department of Education logo
Department of Energy logo
Department of Health and Human Services logo
Department of Homeland Security logo
Department of Transportation logo
Environmental Protection Agency logo
National Aeronautics and Space Administration logo
National Science Foundation logo
US Flag An Official Website of the United States Government