EFFECT OF COLLOIDAL CARRIERS ON THE DISPOSITION AND TISSUE UPTAKE OF DOXORUBICIN .1. CONJUGATION WITH OXIDIZED DEXTRAN PARTICLES

Dextrans are water soluble polymers of glucose, with varying molecular weights. The free hydroxyl groups offer attractive sites for conjugation of drugs with the potential for altering the pharmacokinetic profile of the drug. Doxorubicin is a useful anticancer drug with cardiotoxicity as its most serious side effect. This drug was conjugated to dextran in the following manner. A Schiff's base was formed by incubating oxidized dextran (generated using sodium periodate) with doxorubicin. This mixture was then reduced using sodium borohydride. The conjugates, in the size range of 20 nm, were studied in vitro for the maximum uptake and the release of the drug. In vivo, the conjugated showed a markedly altered disposition profile from the control group. The total body clearance of the drug associated with the conjugate decreased. Additionally, lower concentrations of the drug were found in the heart of animals treated with the conjugates indicating the possibility of reduced cardiotoxicity.