tetano
Editor, Senior Moderator
J Pharm Sci. 2013 Jul 6. doi: 10.1002/jps.23644. [Epub ahead of print]
Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants.
Larson AM, Chen J, Klibanov AM.
Source
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
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.
Copyright ? 2013 Wiley Periodicals, Inc.
KEYWORDS:
antiinfectives, biodegradable polymers, conjugation, drug resistance, inhibition, polymeric drug carrier, polymeric drugs, polymers
PMID:
23832466
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23832466
Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants.
Larson AM, Chen J, Klibanov AM.
Source
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
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.
Copyright ? 2013 Wiley Periodicals, Inc.
KEYWORDS:
antiinfectives, biodegradable polymers, conjugation, drug resistance, inhibition, polymeric drug carrier, polymeric drugs, polymers
PMID:
23832466
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23832466