ABSTRACT
Modern biotechnology has resulted in the production of a great variety of pharmaceutically active proteins (1). Recent statistics show that the Food and Drug Administration (FDA) has approved 130 biotechnology-derived protein medicines and vaccines (2). The unfavorable biopharmaceutical properties of these protein drugs, however, have severely hampered their therapeutic and clinical application. First of
all, oral administration is hardly possible due to chemical and enzymatic degradation in the gastrointestinal tract. Second, proteins have a short half-life after parenteral administration (e.g., intravenous injection), which makes repeated injections or continuous infusion of the protein necessary to obtain a therapeutic effect (3). To overcome these problems, a large number of delivery systems have been designed and evaluated for the release of proteins (4-6). A frequently investigated polymer involved in the design of controlled-release systems for proteins is poly(lactic-co-glycolic acid), or PLGA. This polymer, however, has some intrinsic drawbacks as a protein-releasing matrix. Organic solvents have to be used to prepare pharmaceutical dosage forms (e.g., microspheres), and a low pH might be generated inside the matrix during degradation (7,8). Both factors adversely affect the structural integrity of the protein to be delivered. Moreover, it is difficult to manipulate the release of a protein from PLGA matrices. As an alternative for these biodegradable polyesters, hydrogels (crosslinked, hydrophilic polymeric networks) have been proposed as protein-releasing matrices. This chapter summarizes the work carried out on biodegradable hydrogels based on dextran (dex) and amphiphilic poly(ether ester) multiblock copolymers for protein delivery.
