The proposed studies will create, evaluate and validate the formulation, dosing, pharmacodynamics, cytotoxicity, efficacy and toxicology of a nanoemulsion of a novel cancer stem cell (CSC) cytotoxic drug DHA-SBT-1214. In vitro and in vivo assays using FACS purified CSCs will be used to assess efficacy to kill differentiated tumor cells and CSCs. NE-DHA-SBT-1214 will be administered intravenously (i.v.) to examine drug accumulation and biodistribution over time using validated analytical methods. The goals of this proposal are to fully characterize a novel nanomedicine-based dosage form of DHA-SBT-1214, that addresses multi-drug resistant gastrointesintal cancer (GIC) and other cancers and to prepare pre-IND data required to move this therapy to the clinic. Improving the delivery, accumulation, and pharmacokinetics of the CSC cytotoxic drug while limiting the systemic exposure will minimize cumulative dose-dependent side effects and greatly increase efficacy. For newly diagnosed GIC patients, a majority of whom rapidly progress to a chemoresistant state due to CSCs, the results of this investigation will offer a therapeutic solution that is urgently needed prior to exhausting the clinical options for highly aggressive forms of cancer. The Pre-IND studies outlined will be guided by clinical knowledge and experience as they advance to first-in-human clinical trials.
