Targeted Polymeric Combination Delivery for Treatment of Ovarian Cancer

Award Information
Agency:
Department of Health and Human Services
Amount:
$100,000.00
Program:
STTR
Contract:
1R41CA144818-01A1
Solitcitation Year:
2010
Solicitation Number:
PHS2010-2
Branch:
N/A
Award Year:
2010
Phase:
Phase I
Agency Tracking Number:
R41CA144818
Solicitation Topic Code:
NCI
Small Business Information
UNIVERSITY OF UTAH
615 Arapeen Drive, Suite 302-Y, SALT LAKE CITY, UT, 84108-
Hubzone Owned:
N
Woman Owned:
N
Socially and Economically Disadvantaged:
N
Duns:
828787379
Principal Investigator
 HAMID GHANDEHARI
 (801) 587-1566
 HAMID.GHANDEHARI@PHARM.UTAH.EDU
Business Contact
 DARWIN CHENEY
Phone: (801) 581-6903
Email: ospawards@osp.utah.edu
Research Institution
 University Of Utah
 75 South 2000 East
SALT LAKE CITY, UT, 84112-
 () -
 Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): This Phase I proposal details the rationale and the research plan for the synthesis and characterization of a polymeric delivery system that will deliver two anticancer drugs with diverse mechanisms of action simultaneously into ovarian cancer cells. The delivery system will be composed of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer as the backbone. It is a well characterized, water-soluble, biocompatible, non-immunogenic and non-toxic synthetic polymeric drug carrier. Attached to the backbone will be a geldanamycin analog which has a well known dual mode of action (antiangiogenic and antitumor) and docetaxel, an FDA approved antineoplastic agent which acts by stabilizing microtubules. The drugs will be attached to the backbone via a lysosomally degradable spacer that will allow intracellular release and bioactivity; and (3) a cyclic tripeptide containing ligand that will target the HPMA conjugates to tumor-associated receptors. The novelty of this approach is that the geldanamycin analog and docetaxel, with their different mechanisms of action, will be attached to the same polymer backbone containing a targeting moiety, thereby ensuring the delivery of both the drugs simultaneously to the cancer cells. The aims are three fold: (1) synthesize and physiochemically characterize HPMA copolymers with the geldanamycin analog, docetaxel and the targeting tripeptide in the side chains; (2) characterize the stability and release profile of the HPMA conjugates; and (3) characterize the binding and cytotoxicity of the HPMA conjugates by biological methods in ovarian cancer cell lines. The ultimate goal of this project is the development of an effective and marketable drug combination with novel drug delivery systems for the treatment of ovarian cancer where the drugs are localized at the site of the tumor, adverse effects of chemotherapy are minimized and efficacy maximized. PUBLIC HEALTH RELEVANCE: This Phase I proposal details the rationale and the research plan for the synthesis and characterization of a polymeric delivery system that will deliver two anticancer drugs with diverse mechanisms of action simultaneously into ovarian cancer cells. This combination therapy will minimize the adverse effects of chemotherapy and maximize efficacy, thereby improving significantly the five year survival rate for ovarian cancer patients.

* information listed above is at the time of submission.

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