VESTAR RESEARCH INC.

VESTAR RESEARCH INC. PROPOSES TO DEVELOP PHOSPHOLIPID VESICLE FORMULATIONS (LIPOSOMES) FOR INCORPORATION OF POORLY SOLUBLE AND/OR UNSTABLE ANTICANCER DRUGS INTO AQUEOUS MEDIA ACCEPTABLE FOR INTRAVENOUS USE. THIS METHODOLOGY WILL ENABLE US TO PREPARE AQUEOUS SUSPENSIONS OF ANTITUMOR AGENTS AT CONCENTRATIONS SUFFICIENT FOR THERAPEUTIC STUDIES. THIS IS SIGNIFICANT BECAUSE IT WILL OVERCOME THE SOLUBILITY AND STABILITY LIMITATIONS OF MANY INVESTIGATIONAL SUB-STANCES WITH IMPORTANT ANTITUMOR ACTIVITY. WE WILL OVERCOME THE FORMULATION PROBLEMS ASSOCIATED WITH THESE AGENTS BY DIRECTLY INCORPORATING THEM INTO THE MEMBRANE BILAYERS OF PHOSPHOLIPID VESICLES, THUS MINIMIZING ANY EXPOSURE TO AQUEOUS MEDIA. WE WILL DEMONSTRATE THAT THE MILD CONDITIONS USED FOR THIS METHODOLOGY WILL NOT ALTER THE CHEMICAL STABILITY OF THE FORMULATED DRUG WHILE ATTAINING THE GOAL OF A CONCENTRATED AQUEOUS PREPARATION. THE TECHNOLOGIES TO BE EMPLOYED FOR ACHIEVING THE STATED OBJECTIVES HAVE BEEN DEVELOPED AT VESTAR AND HAVE BEEN PROVEN TO SIGNIFICANTLY PROMOTE THE ACCUMULATION OF VESICLE ASSOCIATED AGENTS IN TUMOR TISSUE. THE PHASE II EFFORT WILL BUILD ON THE RESULTS OF THE PROPOSED WORK BY DEMONSTRATING THE ABILITY OF OUR VESICLE FORMULATIONS TO INCREASE THE LEVELS OF THERAPEUTIC AGENTS DELIVERED TO NEOPLASTIC TISSUE AND THUS ENHANCE ANTITUMOR ACTIVITY. FOR MOST COMPOUNDS IT SHOULD BE POSSIBLE TO ACCOMPLISH THIS WITHOUT INCREASING, AND MOST PROBABLY DECREASING, SYSTEMIC TOXICITY. THEREFORE, VESICLE PREPARATIONS OF POORLY SOLUBLE AND/OR UNSTABLE SUBSTANCES HAVE THE CLEAR POTENTIAL FOR SIGNIFICANTLY