No abstract

Naturally occurring polymers of N-acetylneuraminic acid (polysialic acids) are biodegradable, highly hydrophilic and have no known receptors in the body. Following intravenous injection, polysialic acids exhibit long half-lives in the blood circulation and have therefore been proposed as carriers of short-lived drugs and small peptides. In addition, shorter-chain polysialic acids can be used as a means to increase the circulatory half-life of proteins and thus serve as an alternative to the nonbiodegradable monomethoxypoly(ethylene glycol). Recent work has shown that covalent coupling of a low molecular weight polysialic acid (colominic acid) to catalase and asparaginase leads to a considerable increase of enzyme stability in the presence of proteolytic enzymes or blood plasma. Comparative studies in vivo with polysialylated and intact asparaginase revealed that polysialylation significantly increases the half-life of the enzyme. The highly hydrophilic and innocuous nature of polysialic acids renders them suitable as a means to prolong the circulation of peptides and proteins.

A number of bacterial polysialic acids were injected intravenously into mice. Half-lives (up to 40 hf in the blood circulatron were dependent on the polysialic acid used, increased by deacylation of their phospholipid moiety, decreased with shorter chain derivatives and appeared to be dose independent. A model drug (fluorescein) covalently coupled to a polysialic acid was found to assume the half-life of its carrier. Results suggest that intact or deacylated polysialic acids and shorter chain derivatives can be used to augment the half-lives of drugs, small peptides, proteins and drug delivery systems in the blood circulation, thus prolonging their pharmacological action,

No abstract

No abstract