Approximately 17,000 Americans are newly diagnosed with malignant brain tumors each year, and more than 13,000 die annually from this disease. Chemotherapy of brain tumors is hampered by the inability of most antitumor agents to cross the blood-brain barrier. Cornerstone Pharmaceuticals, Inc. proposes to formulate a tumor-targeting drug delivery system, based on a proprietary lipid technology. Microbubble particles prepared from this lipid mixture cross the blood-brain barrier and accumulate with high selectivity to implanted brain tumors in rats. However, no method currently exists to prepare these microbubble particles on a commercial scale. We have recently prepared lipid nanoparticles, using the lipid mixture which comprises microbubble particles, by high-pressure homogenization, a method amenable to formulation and manufacturing. In this Phase I proposal, we propose to test whether central nervous system tumor cells take up lipid nanoparticles, determine conditions for stable loading of chemotherapeutic agents in these lipid nanoparticles, and evaluate the cytotoxicity of drug-loaded lipid nanoparticles against cultured central nervous system tumor cells. If we are successful in our goals, we will formulate antitumor drugs for clinical use, test antitumor efficacy of our drug formulations in vivo, and optimize scale-up and manufacturing conditions of these drug formulations in Phase II.
Thesaurus Terms: antineoplastic, blood brain barrier, brain neoplasm, drug delivery system, lipid, microcapsule, nanotechnology, technology /technique development drug design /synthesis /production flow cytometry
