Immobilized adriamycin: toxic potential in vivo and in vitro.
We report experiments which test the toxicity of a new potential therapeutic agent, agarose-bound adriamycin (ImA). In C57Bl/6N mice this preparation is almost completely devoid of untoward effects when administered intraperitoneally; ImA lacks all the usual toxic repercussions of free adriamycin including abdominal adhesions, inflammatory peritonitis, weight loss and cardiotoxicity. The immobilized adriamycin is also inactive in a fetal mouse heart model of cardiac toxicity. This lack of toxicity is not due to an intrinsic inactivity of the drug, however, since previous studies have shown that polymer-bound adriamycin can kill actively dividing cells. We also show here that the immobilized drug can undergo redox reactions and interact with enzymes from isolated respiratory chain preparations, so the lack of cardiac toxicity in vivo is most likely due to inaccessibility of the target. These results suggest that polymer immobilized adriamycin lacks the toxicity of the parent compound and may present a useful approach to regional chemotherapy.
Department of Pharmacology and Vermont Regional Cancer Center, University of Vermont, College of Medicine, Burlington.
M P
MP
Hacker
J S
JS
Lazo
C A
CA
Pritsos
T R
TR
Tritton
D000818:Animals; D002417:Cattle; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D004343:Drug Implants; D005260:Female; D005333:Fetus / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011247:Pregnancy
D004343:Drug Implants; D004317:Doxorubicin