Journal article
Critical Design Features of Phenyl Carboxylate-Containing Polymer Microbicides
Antimicrobial agents and chemotherapy, v 50(9), pp 3081-3089
Sep 2006
PMID: 16940105
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Recent studies of cellulose-based polymers substituted with carboxylic acids like cellulose acetate phthalate (CAP) have demonstrated the utility of using carboxylic acid groups instead of the more common sulfate or sulfonate moieties. However, the pK
a
of the free carboxylic acid group is very important and needs careful selection. In a polymer like CAP the pK
a
is approximately 5.28. This means that under the low pH conditions found in the vaginal lumen, CAP would be only minimally soluble and the carboxylic acid would not be fully dissociated. These issues can be overcome by substitution of the cellulose backbone with a moiety whose free carboxylic acid group(s) has a lower pK
a
. Hydroxypropyl methylcellulose trimellitate (HPMCT) is structurally similar to CAP; however, its free carboxylic acids have pK
a
s of 3.84 and 5.2. HPMCT, therefore, remains soluble and molecularly dispersed at a much lower pH than CAP. In this study, we measured the difference in solubility and dissociation between CAP and HPMCT and the effect these parameters might have on antiviral efficacy. Further experiments revealed that the degree of acid substitution of the cellulose backbone can significantly impact the overall efficacy of the polymer, thereby demonstrating the need to optimize any prospective polymer microbicide with respect to pH considerations and the degree of acid substitution. In addition, we have found HPMCT to be a potent inhibitor of CXCR4, CCR5, and dual tropic strains of human immunodeficiency virus in peripheral blood mononuclear cells. Therefore, the data presented herein strongly support further evaluation of an optimized HPMCT variant as a candidate microbicide.
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Details
- Title
- Critical Design Features of Phenyl Carboxylate-Containing Polymer Microbicides
- Creators
- Robert F Rando - Novaflux Biosciences, Inc., Princeton, New Jersey 08540Sakae Obara - Novaflux Biosciences, Inc., Princeton, New Jersey 08540Mark C Osterling - Novaflux Biosciences, Inc., Princeton, New Jersey 08540Marie Mankowski - Novaflux Biosciences, Inc., Princeton, New Jersey 08540Shendra R Miller - Novaflux Biosciences, Inc., Princeton, New Jersey 08540Mary L Ferguson - Novaflux Biosciences, Inc., Princeton, New Jersey 08540Fred C Krebs - Novaflux Biosciences, Inc., Princeton, New Jersey 08540Brian Wigdahl - Novaflux Biosciences, Inc., Princeton, New Jersey 08540Mohamed Labib - Novaflux Biosciences, Inc., Princeton, New Jersey 08540Hiroyasu Kokubo - Novaflux Biosciences, Inc., Princeton, New Jersey 08540
- Publication Details
- Antimicrobial agents and chemotherapy, v 50(9), pp 3081-3089
- Publisher
- American Society for Microbiology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000240297000026
- Scopus ID
- 2-s2.0-33748681545
- Other Identifier
- 991014877785604721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Microbiology
- Pharmacology & Pharmacy