Projects per year
Abstract
Colistin is an amphiphilic antibiotic that has re-emerged into clinical use due to the increasing prevalence of difficult-to-treat Gram-negative infections. The existence of self-assembling colloids in solutions of colistin and its derivative prodrug, colistin methanesulfonate (CMS), was investigated. Colistin and CMS reduced the aira??water interfacial tension, and dynamic light scattering (DLS) studies showed the existence of 2.07 A? 0.3 nm aggregates above 1.5 mM for colistin and of 1.98 A? 0.36 nm aggregates for CMS above 3.5 mM (mean A? SD). Above the respective critical micelle concentrations (CMC) the solubility of azithromycin, a hydrophobic antibiotic, increased approximately linearly with increasing surfactant concentration (5:1 mol ratio colistin:azithromycin), suggestive of hydrophobic domains within the micellar cores. Rapid conversion of CMS to colistin occurred below the CMC (60 over 48 h), while conversion above the CMC was less than 1 . The formation of colistin and CMS micelles demonstrated in this study is the proposed mechanism for solubilization of azithromycin and the concentration-dependent stability of CM
Original language | English |
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Pages (from-to) | 4836 - 4840 |
Number of pages | 5 |
Journal | Journal of Physical Chemistry B |
Volume | 114 |
DOIs | |
Publication status | Published - 2010 |
Projects
- 2 Finished
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Optimizing dosing of colistin for infections resistant to all other antibiotics.
Nation, R. (Primary Chief Investigator (PCI)) & Li, J. (Chief Investigator (CI))
NIH - National Institutes of Health (United States of America)
15/09/08 → 31/08/12
Project: Research
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Targeting MD hetero-resistant Gram-negatives: PK/PD for rational combinations.
Nation, R. (Primary Chief Investigator (PCI)), Li, J. (Chief Investigator (CI)), Forrest, A. (Partner Investigator (PI)), Paterson, D. L. (Partner Investigator (PI)) & Tsuji, B. T. (Partner Investigator (PI))
NIH - National Institutes of Health (United States of America)
15/07/08 → 30/06/12
Project: Research