Preclinical experiences with magnetic drug targeting: tolerance and efficacy.
Although site-specific direction of drugs within an organism would benefit patients with many diseases, active drug targeting is clinically not yet possible. To overcome some of the problems associated with active drug targeting, we have developed a magnetic fluid to which drugs, cytokines, and other molecules can be chemically bound to enable those agents to be directed within an organism by high-energy magnetic fields. In the first part of this study, various concentrations of the magnetic fluid were tested in rats and immunosuppressed nude mice with regard to subjective and objective tolerance. In the second part, the same parameters were evaluated after administration of the ferrofluid to which epirubicin (4'-epidoxorubicin) was chemically bound. Finally, two forms of therapy with the magnetic fluid were tested: tumor treatment by mechanical occlusion with the ferrofluid in high concentrations; and magnetic drug targeting, using small amounts of the ferrofluid as a vehicle to concentrate epirubicin locally in tumors. As a result, the ferrofluid did not cause major laboratory abnormalities; there was no LD50. With very high concentrations of the ferrofluid, animals showed lethargy for 1-2 days. There were no intolerances with the epirubicin-bound ferrofluid as well. Both forms of treatment led to complete tumor responses in an experimental human kidney as well as in a xenotransplanted colon carcinoma model. Thus, the magnetic fluid is a safe agent, which can be used in different ways for local forms of cancer treatment in conjunction with high-energy magnetic fields.
Lübbe
A S
AS
Department of Medicine (Hematology and Oncology), Virchow Medical School, Humboldt-Universität zu Berlin, Germany.
Bergemann
C
C
Huhnt
W
W
Fricke
T
T
Riess
H
H
Brock
J W
JW
Huhn
D
D
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D016503:Drug Delivery Systems; D004621:Embolization, Therapeutic / Q000379:methods; D015251:Epirubicin / Q000008:administration & dosage* / Q000009:adverse effects; D008280:Magnetics / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000903:Antibiotics, Antineoplastic; D015251:Epirubicin