PRECLINICAL EXPERIENCES WITH MAGNETIC DRUG TARGETING - TOLERANCE AND EFFICACY

Although site-specific direction of drugs within an organism would ben efit patients with many diseases, active drug targeting is clinically not yet possible. To overcome some of the problems associated with act ive drug targeting, we have developed a magnetic fluid to which drugs, cytokines, and other molecules can be chemically bound to enable thos e agents to be directed within an organism by high-energy magnetic fie lds. In the first part of this study, various concentrations of the ma gnetic fluid were tested in rats and immunosuppressed nude mice with r egard to subjective and objective tolerance. In the second part, the s ame parameters were evaluated after administration of the ferrofluid t o which epirubicin (4'-epidoxorubicin) was chemically)ly bound. Finall y, two forms of therapy with the magnetic fluid were tested: tumor tre atment by mechanical occlusion with the ferrofluid in high concentrati ons; and magnetic drug targeting, using small amounts of the ferroflui d as a vehicle to concentrate epirubicin locally in tumors. As a resul t, the ferrofluid did not cause major laboratory abnormalities; there was no LD(50). With very high concentrations of the ferrofluid, animal s showed lethargy for 1-2 days. There were no intolerances with the ep irubicin-bound ferrofluid as well. Both forms of treatment led to comp lete tumor responses in an experimental human kidney as well as in a x enotransplanted colon carcinoma model. Thus, the magnetic fluid is a s afe agent, which can be used in different ways for local forms of canc er treatment in conjunction with high-energy magnetic fields.