Anthracycline antibiotics supported on water-soluble polysaccharides: Synthesis and physicochemical characterization

Daunomycin and adriamycin, two potent anthracycline antibiotics, have been covalently bound to the biocompatible polysaccharides sodium hyaluronate and carboxymethylcellulose. The water-soluble conjugates have been investigated by means of spectroscopic and hydrodynamic techniques. The conformation properties of the polysaccharide chains are not dramatically affected upon derivatization. The acidic dissociation constants of the polymer-supported anthracyclines are decreased as a result of polyelectrolyte effects from the negatively charged backbone. The polymeric drugs are able to bind efficiently biologically relevant metal ions, in particular Cu++. The binding stoichiometry, with reference to the parent anthracyclines, is somewhat changed under similar experimental conditions. The equilibrium constants for Cu++ binding show on the other hand characteristics well related to the corresponding properties of the original compounds. In addition, the redox potentials of the drugs remain pr...