Polysialic acids: potential in improving the stability and pharmacokinetics of proteins and other therapeutics

Naturally occurring polymers of N-acetylneuraminic acid (polysialic acids) are biodegradable, highly hydrophilic and have no known receptors in the bo dy. Following intravenous injection, polysialic acids exhibit long half-liv es in the blood circulation and have therefore been proposed as carriers of short-lived drugs and small peptides. In addition, shorter-chain polysiali c acids can be used as a means to increase the circulatory half-life of pro teins and thus serve as an alternative to the nonbiodegradable monomethoxyp oly(ethylene glycol). Recent work has shown that covalent coupling of a low molecular weight polysialic acid (colominic acid) to catalase and asparagi nase leads to a considerable increase of enzyme stability in the presence o f proteolytic enzymes or blood plasma. Comparative studies in vivo with pol ysialylated and intact asparaginase revealed that polysialylation significa ntly increases the half-life of the enzyme. The highly hydrophilic and inno cuous nature of polysialic acids renders them suitable as a means to prolon g the circulation of peptides and proteins.