Drug delivery compositions are provided having proteins and biodegradable polymers that may be used for controlled and long term release of proteins into a biological environment. According to some embodiments, the drug delivery composition may be provided with at least a protein and a biodegradable polymer possessing at least two different functional groups selected from the group of chosen among carboxyl, ester, amine, amide, thiol, thioester or hydroxyl groups pendant to the main polymer chain whereby the composition absorbs between 5-10% w/w water when exposed to physiological conditions for at least 20 days. A drug delivery system for controlled protein release which includes the drug delivery composition is also provided whereby the drug delivery system may be in the form of microparticles, films, coatings, fibers, pellets, cylinders, discs, implants, microcapsules, microspheres, nanospheres, wafers, micelles, liposomes or woven or non-woven fabrics.