[Biodegradable polymeric derivatives of polypeptide drugs for targeting]

Relatively short polymer chains with lower critical solution temperatures were immobilized on protein macromolecules to obtain biodegradable polymeric derivatives of proteins (including those for heat-inactivated targeting of polypeptide drugs). Addition of a derivative to a multicomponent biological system and heating of the target to a temperature in excess of the lower critical solution temperature was followed by the carrier release into a separate phase and the transportation of the bound protein to the target. The protein molecule served as a biodegradable region and was progressively hydrolyzed, with the formation of low-molecular-weight fragments. These fragments were readily eliminated from the organism. The physiological activity of immobilized serum albumin was independent of the number of attached chains in the polymer carrier (the constant of bilirubin binding equaled 10 M(-1)). The biodegradation of synthetic systems, caused by alpha-chymotrypsin, was also studied. The more polymer chains were attached to serum albumin, the greater was the resistance of the protein to enzymatic hydrolysis.