Document Detail


High antimicrobial effectiveness with low hemolytic and cytotoxic activity for PEG/quaternary copolyoxetanes.
MedLine Citation:
PMID:  24422429     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The alkyl chain length of quaternary ammonium/PEG copolyoxetanes has been varied to discern effects on solution antimicrobial efficacy, hemolytic activity and cytotoxicity. Monomers 3-((4-bromobutoxy)methyl)-3-methyloxetane (BBOx) and 3-((2-(2-methoxyethoxy)ethoxy)methyl)-3-methyloxetane (ME2Ox) were used to prepare precursor P[(BBOx)(ME2Ox)-50:50-4 kDa] copolyoxetane via ring opening polymerization. The 1:1 copolymer composition and Mn (4 kDa) were confirmed by 1H-NMR spectroscopy. After C-Br substitution by a series of tertiary amines, ionic liquid Cx-50 copolyoxetanes were obtained, where 50 is the mole percent of quaternary repeat units and 'x' is quaternary alkyl chain length (2, 6, 8, 10, 12, 14 or 16 carbons). Modulated differential scanning calorimetry (MDSC) studies showed Tg's between -40 and -60 °C and melting endotherms for C14-50 and C16-50. Minimum inhibitory concentrations (MIC) were determined for Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. A systematic dependence of MIC on alkyl chain length was found. The most effective antimicrobials were in the C6-50 to C12-50 range. C8-50 had better overall performance with MICs of 4 μg/mL, E. coli; 2 μg/mL, S. aureus; and 24 μg/mL, P. aeruginosa. At 5 × MIC, C8-50 effected >99% kill in 1 hr against S. aureus, E. coli and P. aeruginosa challenges of 108 cfu/mL; log reductions (1 hr) were 7, 3, and 5 respectively. To provide additional insight into polycation interactions with bacterial membranes, a geometric model based on the dimensions of E. coli is described that provides an estimate of the maximum number of polycations that can chemisorb. Chain dimensions were estimated for polycation C8-50 with a molecular weight of 5 kDa. Considering the approximations for polycation chemisorption (PCC), it is surprising that a calculation based on geometric considerations gives a C8-50 concentration within a factor of two of the MIC, 4.0 (±1.2) µg/mL for E. coli. Cx-50 copolyoxetane cytotoxicity was low for human red blood cells, human dermal fibroblasts (HDF), and human foreskin fibroblasts (HFF). Selectivities for bacterial kill over cell lysis were among the highest ever reported for polycations indicating good prospects for biocompatibility.
Authors:
Allison King; Souvik Chakrabarty; Wei Zhang; Xiaomei Zeng; Dennis E Ohman; Lynn F Wood; Sheena Abraham; Raj Rao; Kenneth J Wynne
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-1-14
Journal Detail:
Title:  Biomacromolecules     Volume:  -     ISSN:  1526-4602     ISO Abbreviation:  Biomacromolecules     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-1-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100892849     Medline TA:  Biomacromolecules     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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