DESCRIPTION: Topoisomerase inhibition (Ti) is an area of emerging prominence in the chemotherapy of cancer. Tigen Pharmaceuticals in collaboration with Dr. Giovanella of the Stehlin Foundation for Cancer Research now plan to explore the commercial development of novel camptothecin-class topoisomerase inhibitors and patented delivery formulations (T.G. Burke, U.S. Patent 5,552156). The research objective of this grant application is to explore the potential of stable camptothecin drug formulations to potentiate anticancer activities. The project involves the pharmaceutical formulation and biological evaluation of lipophilic camptothecins delivered in liposomal carriers. The liposomal vehicles stabilize the active lactone form of the highly potent medications which they carry. Several different highly active lipophilic camptothecins will be studied. The role of liposomal lipid composition in affecting drug stability, particle stability, and encapsulation efficiency will be explored. Evaluation of the in vitro anticancer activities of the liposomal formulations against cultures of nine human cancers representative of the most common forms of human cancer (ovary, pancreas, colon, lung, breast, melanoma, and leukemia) will be carried out. Mechanistic information will be sought concerning the details by which liposomal formulations potentiate the activities of camptothecins. Evaluation of the in vivo antitumor activities and tumor localization of the various camptothecin liposomal formulations against human xenografts will be carried out. The pharmacokinetics/ pharmacodynamic aspects of liposomal camptothecin delivery in animal models will also be evaluated. Using their analytical methods, investigators will seek to identify liposomal formulations which deliver high levels of active lactone drug to tumorous tissue and thereby potentiate anticancer activity. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE
|Effective start/end date||5/6/98 → 8/31/04|
- Cancer Research
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