TY - JOUR
T1 - Self-assembly behavior of colistin and its prodrug colistin methanesulfonate: implications for solution stability and solubilization
AU - Wallace, Stephanie Jean
AU - Li, Jian
AU - Nation, Roger Leigh
AU - Prankerd, Richard John
AU - Velkov, Tony
AU - Boyd, Benjamin James
PY - 2010
Y1 - 2010
N2 - 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
AB - 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
U2 - 10.1021/jp100458x
DO - 10.1021/jp100458x
M3 - Article
C2 - 20302384
VL - 114
SP - 4836
EP - 4840
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
SN - 1520-6106
ER -