Self-Assembly Behavior of Colistin and Its Prodrug Colistin Methanesulfonate: Implications for Solution Stability and Solubilization
| Autor: | Richard John Prankerd, Roger L. Nation, Jian Li, Tony Velkov, Stephanie Jean Wallace, Benjamin James Boyd |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Azithromycin
Micelle Article Surface-Active Agents Dynamic light scattering Pulmonary surfactant polycyclic compounds Materials Chemistry medicine Prodrugs Physical and Theoretical Chemistry Solubility Micelles health care economics and organizations Aqueous solution Chromatography Colistin Chemistry biochemical phenomena metabolism and nutrition Prodrug bacterial infections and mycoses Anti-Bacterial Agents Surfaces Coatings and Films Solutions lipids (amino acids peptides and proteins) Polymyxin B medicine.drug |
| Zdroj: | The Journal of Physical Chemistry B. 114:4836-4840 |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/jp100458x |
| Popis: | 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 air-water interfacial tension, and dynamic light scattering (DLS) studies showed the existence of 2.07 +/- 0.3 nm aggregates above 1.5 mM for colistin and of 1.98 +/- 0.36 nm aggregates for CMS above 3.5 mM (mean +/- 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 CMS. |
| Databáze: | OpenAIRE |
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