STABLE CAMPTOTHECIN FORMULATIONS FOR CANCER TREATMENT

Project: Research project

Project Details

Description

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
StatusFinished
Effective start/end date5/6/988/31/04

Funding

  • National Cancer Institute: $220,324.00

ASJC

  • Oncology
  • Cancer Research

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