Abstract
Modern biotechnology has realized to produce polypeptide drugs on a large scale. Although some of them need controlled release because of the too short half-times in the blood, any good systems for their sustained release are not yet available. The major reason is a high susceptibility of polypeptides to denaturation. To develop an effective system for the sustained release of polypeptides, we take advantage of polyion complexation that is defined as complex formation between two oppositely charged polyelectrolytes. Polypeptides are either positively or negatively charged in aqueous solution unless the solution pH is equal to the isoelectric point. Because the polymeric carrier being used for injectable drugs should be resorbable, we chosed gelatin as a carrier of polypeptide drugs. Both negatively and positively-charged gelatins are commercially available. As an example we describe here a combination of negatively-charged gelatin with basic fibroblast growth factor (bFGF) that is a cell growth factor having an isoelectric point of 9.6. Upon mixing in aqueous solution, these two biomacromolecules form a polyion complex, allowing the sustained release of bFGF when injected in animals. In vivo studies revealed that the bFGF molecules released in the body still maintained the biological activities as a cell growth factor. This new drug delivery system was applied to vascularization and regeneration of cartilage and bone for mice and rabbits.
