ABSTRACT
Trypsin was immobilized on polymeric carriers with low critical solution temperature (LCST). Homopolymer of N,N-diethylacrylamide (DEAA), random copolymers of DEAA and acrylamide (AA), and block copolymers polyDEAA-polyAA were used as the carriers. It was shown that at a temperature above LCST all carriers have a conformation change and trypsin's polymeric derivatives precipitate. The maximal activity after phase transition keeps trypsin, immobilized on polyDEAA block in polyDEAA-polyAA block-copolymer.
Subject(s)
Acrylic Resins/chemistry , Enzymes, Immobilized/chemistry , Trypsin/chemistry , Animals , Catalysis , Hot TemperatureABSTRACT
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.
Subject(s)
Acrylamides/chemistry , Drug Carriers/chemistry , Peptides/chemistry , Pharmaceutical Preparations/chemistry , Polymers/chemistry , Bilirubin/chemistry , Biotransformation , Serum Albumin/chemistry , TemperatureABSTRACT
Experiments on animals showed that native proteins may diffuse into the blood flow after oral administration of diluted protein solutions. An in vitro study led us to hypothesize that treatment with diluted solutions is accompanied by a decrease in the rate of protein proteolysis and accelerated protein diffusion through the intestinal mucosa.