Synthesis and physical characterization of poly(ethylene glycol)-gelatin conjugates.

Poly(ethylene glycol) (PEG) with the terminal group of active ester was coupled to the amino group of gelatin to prepare PEG-grafted gelatin (PEG-gelatin). The affinity chromatographic study revealed that the PEG-gelatin with high degrees of PEGylation did not adsorb onto the gelatin affinity column, in remarked contrast to gelatin alone and the PEG-gelatin with low PEGylation degrees. The former PEG-gelatin showed a critical micelle concentration while it had the apparent molecular size of about 100 nm and a surface charge of almost zero. These findings indicate that the PEG-gelatin formed a micelle structure of which the surface is covered with PEG molecules grafted. When the body distribution of 125I-labeled gelatin and PEG-gelatin after intravenous injection was evaluated, the radioactivity of micellar PEG-gelatin was retained in the blood circulation compared with that of gelatin and the PEG-gelatin of no micelle formation. At the same PEGylation degree, the blood concentration was significantly higher for the PEG-gelatin prepared from PEG with a molecular weight of 12 000 than that of molecular weights of 2000 and 5000. It is concluded that the PEG-gelatin is a drug carrier with a micelle structure which retains in the blood circulation.