Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10162673 | Journal of Pharmaceutical Sciences | 2013 | 10 Pages |
Abstract
By attaching multiple copies of the influenza M2 ion channel inhibitors amantadine (1) and rimantadine (2) to polymeric chains, we endeavored to recover their potency in inhibiting drug-resistant influenza viruses. Depending on loading densities, as well as the nature of the drug, the polymer, and the spacer arm, polymer-conjugated drugs were up to 30-fold more potent inhibitors of drug-resistant strains than their monomeric parents. In particular, a 20% loading density and a short linker group on the negatively charged poly-L-glutamate resulted in one of the most potent inhibitors for 2's conjugates against drug-resistant influenza strains. Although full recovery of the inhibitory action against drug-resistant strains was not achieved, this study may be a step toward salvaging anti-influenza drugs that are no longer effective. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2450-2459, 2013
Keywords
Related Topics
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Alyssa M. Larson, Jianzhu Chen, Alexander M. Klibanov,