Prolongation of drug release by covalent bonding of drugs to serum albumin microbeads.

Reaction conditions for the covalent bonding of 5'-deoxy-5-fluorouridine to serum albumin microbeads by means of a water-soluble carbodiimide were studied. Optimum coupling of dFUR to the microbeads occurred when pure water was used as solvent. There was no significant difference in the bonding efficiency for microbeads prepared at different stirring speeds, and there was a limit to the amount of dFUR that could be bound with increasing reaction time. Yields were low possibly because of competing coupling reactions involving carbodiimide and other reactive groups in the protein. The release of dFUR from dFUR-bound microbeads was slow and biexponential. The fraction of dFUR bound in the interior of the microbeads increased with increasing reaction time.