Macromolecular prodrugs of ribavirin combat side effects and toxicity with no loss of activity of the drug

Chemi-enzymatic synthesis of ribavirin acrylate and subsequent RAFT co-polymerization with acrylic acid afforded a formulation of a broad spectrum antiviral drug which avoids accumulation in erythrocytes, the origin of the main side effect of ribavirin. In cultured macrophages the macromolecular pro...

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Published inChemical communications (Cambridge, England) Vol. 49; no. 26; pp. 2643 - 2645
Main Authors Kryger, Mille B. L, Wohl, Benjamin M, Smith, Anton A. A, Zelikin, Alexander N
Format Journal Article
LanguageEnglish
Published England 04.04.2013
Subjects
Acrylates - chemical synthesis
Acrylates - chemistry
Acrylates - pharmacology
Animals
Cells, Cultured
Dose-Response Relationship, Drug
Macromolecular Substances - chemical synthesis
Macromolecular Substances - chemistry
Macromolecular Substances - pharmacology
Macrophages - drug effects
Macrophages - metabolism
Mice
Molecular Conformation
Nitric Oxide - antagonists & inhibitors
Nitric Oxide - biosynthesis
Prodrugs - chemical synthesis
Prodrugs - chemistry
Prodrugs - pharmacology
Ribavirin - chemical synthesis
Ribavirin - chemistry
Ribavirin - pharmacology
Structure-Activity Relationship
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Summary:Chemi-enzymatic synthesis of ribavirin acrylate and subsequent RAFT co-polymerization with acrylic acid afforded a formulation of a broad spectrum antiviral drug which avoids accumulation in erythrocytes, the origin of the main side effect of ribavirin. In cultured macrophages the macromolecular prodrugs exhibited decreased toxicity while maintaining the anti-inflammatory action of ribavirin. Acrylate-based prodrugs of ribavirin afford well-defined synthetic polymers for safe delivery of this antiviral therapeutic.
Bibliography:10.1039/c3cc00315a
Electronic supplementary information (ESI) available: Experimental details and polymer characterization is available. See DOI
RAW264.7 cells were a generous gift from Søren Kragh Moestrup laboratory, Aarhus University. Erythrocytes were supplied generously by Skejby Hospital blood bank. Thomas Hussmann (Aarhus University) is acknowledged for laboratory assistance. This work is supported by a grant from the Lundbeck Foundation and Sapere Aude Starting Grant from the Danish Council for Independent Research, Technology and Production Sciences, Denmark.
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ISSN:1359-7345
1364-548X
DOI:10.1039/c3cc00315a