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| Grant Number: | 1R41HL068492-01A1 |
| PI Name: | SUBBIAH, RAVI M. |
| PI Email: | mtrsubbiah@yahoo.com |
| PI Title: | PROF. OF EXPER. MEDICINE & PATH. |
| Project Title: | Targeted Delivery of Estrogen in Menopause |
Abstract: DESCRIPTION (provided by applicant): In postmenopausal women, coronary artery disease (CAD) is the leading cause of death. Estrogen replacement therapy appears to offer considerable protection against CAD in postmenopausal women. However, there is great concern about risk for breast and endometrial cancer after long-term estrogen use in these women. The activation of estrogen receptors and subsequent genomic effects in terms of cell growth appears to play a significant role in estrogen-related carcinogenesis. Our laboratory has been interested in achieving a differential effect of estrogens by differential delivery to cells. We hypothesize that desired cardioprotective benefits of estrogens (without carcinogenic effects) can be achieved either through a) macrophages targeted for preferential delivery of hydrophobic estrogen acetylated LDL (ac-LDL) complexes to atherosclerotic tissues or b) by conjugating these estrogens into lipid microspheres or by coating lipoprotein/estrogen complexes with functionalized (Fc) dextran, both of which have been used for preferential uptake by endothelial cells. Phase I will determine a) whether i.v. administered hydrophobic estrogens will associate with LDL; b) tissue distribution and the feasibility of macrophage-targeted (MT) and endothelium-targeted (ET) liposomal preparation of hydrophobic estrogen derivatives for differential delivery to macrophages or endothelium and c) whether ET and MT are functionally active. Phase II will deal with their in vivo effects on atherogenic indices and suitable lipoprotein-like carriers and enhancers for use as transdermal patch.
Thesaurus Terms:
cardiovascular agent, cardiovascular pharmacology, coronary disorder, drug delivery system, estrogen, low density lipoprotein, menopause
atherosclerotic plaque, estrogen receptor, ethanol, hormone related neoplasm /cancer, hormone therapy, intravenous administration, liposome, macrophage, topical drug application, vascular endothelium
| Institution: | MOLECULAR DIAGNOSTICS LABORATORIES, INC. |
| 3130 HIGHLAND AVE, STE 3315 | |
| CINCINNATI, OH 45219 | |
| Fiscal Year: | 2002 |
| Department: | |
| Project Start: | 30-SEP-2002 |
| Project End: | 29-SEP-2003 |
| ICD: | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE |
| IRG: | ZRG1 |