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Cell Mol Life Sci. 2000 Dec;57(13-14):1964-9.

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

Author information

1
Centre for Drug Delivery Research School of Pharmacy, University of London, United Kingdom. gregoriadis@cua.ulsop.ac.uk

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.

PMID:
11215521
DOI:
10.1007/PL00000676
[Indexed for MEDLINE]

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