We propose to develop targetable formulations of promising anti-cancer agents (DNA-intercalating agents, Cucurbitacin derivatives, and Swainsonine) which have undergone evaluation by NCI's in vitro anticancer screening and are considered to possess high therapeutic potential, but showed insufficient bioavailability, in vivo instability, or inability to achieve therapeutic levels in tumors without prohibitive systemic toxicity. We will use innovative drug-formulation and -delivery technologies, specifically tumor targeting, to overcome these problems. Based on the physical properties of each agent, we will first screen these compounds to evaluate their potential for liposome or nanoparticle formulation. We will formulate and optimize these compounds using HERMES' innovative liposome design and PolySol (TM) technology. The most successful formulations will be selected for preparing targetable formulations with tumor-specific antibodies, e.g., antiHER2. The interaction of these antibody-directed formulations with target cells will be investigated. Pharmacokinetic studies of potentially useful formulations will be completed during the second budgeted year. The optimized targetable liposomes or nanosol carriers are expected to minimize nonspecific toxicities of these drugs against normal tissues. Internalization of these novel formulations by tumor targets will dramatically increase the rate of successful delivery of the therapeutic drugs and thus enhance therapeutic efficacy.

Proposed Commercial Applications

There is an immense need for better cancer treatment, and so is the market potential for more effiacious, less toxic cancer chemotherapy. The proposed formulation approach is expected to yield marketable pharmaceutical products in the form of new generation anticancer chemotherapeutics via better tumor cell targeting. In doing so it also enhances the drug screening effort by Developmental Therapeutics Program.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
5R43CA086156-02
Application #
6342231
Study Section
Special Emphasis Panel (ZCA1-SRRB-Y (J4))
Program Officer
Fu, Yali
Project Start
2000-08-01
Project End
2002-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
2
Fiscal Year
2001
Total Cost
$250,290
Indirect Cost
Name
Hermes Biosciences, Inc.
Department
Type
DUNS #
019116545
City
South San Francisco
State
CA
Country
United States
Zip Code
94080