Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 300, Issue 1-2, Pages 125-130Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2005.06.007
Keywords
polysialic acid; peptide drugs; protein drugs; insulin interferon; erythropoietin; granulocyte colony stimulating factor
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Peptide and protein drugs are a growing class of therapeutics. However, their effective application in the clinic is compromised by problems, for instance proteolysis in the circulating blood, premature clearance through the kidneys, and immunogenicity. A number of approaches have been used to circumvent such shortcomings including changes in the primary peptide structure, entrapment into nanoparticles (e.g. liposomes) and conjugation to polymers. Polysialylation, namely, conjugation of peptides and proteins to the naturally occurring, biodegradable alpha-(2 -> 8) linked polysialic acid is a recent development, which promises to be at least as effective as PEGylation but without its potential toxicity. Polysialylation of a range of peptide and protein therapeutics has led to markedly reduced proteolysis, retention of their activity in vivo, prolongation of their half-life in the circulation and reduction in immunogenicity and antigenicity. It is anticipated that polysialylation will lead to a new generation of peptide and protein constructs with significantly improved pharmacological profiles. (c) 2005 Elsevier B.V. All rights reserved.
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