Nontoxic antimicrobial micellar systems based on mono- and di-cationic Dabco-surfactants and furazolidone: Structure-solubilization properties relationships

Abstract

Self-assembly and solubilization properties of amphiphilic mono- and bisquaternized derivatives of 1,4-diazabicyclo[2.2.2]octane (mono-CS-n and di-CS-n, where CS cationic surfactant, n=12, 14, 16, 18) was investigated by nuclear magnetic resonance with magnetic field pulse gradient. The influence of Dabco-surfactant structure (head group and length of alkyl chains) on critical micelle concentration and aggregation number of micelles was studied. The CMC of mono-CS-n are lower than CMC of di-CS-n. The aggregation numbers of mono-CS-n micelles are higher than for di-CS-n micelles. The solubilization capacity of mono-CS-n is higher than di-CS-n. The solubilization capacity of mono-CS-16 is 2.5 times higher than CTAB in the case of Orange OT as a solute, and it is close to CTAB in the case of Sudan I. The solubility of a poorly water-soluble antibacterial drug furazolidone was improved by micellar solubilization based on mono- and di-Dabco-surfactants. Mono-CS-n is the best solubilizing agents toward furazolidone. The use of mixed composition mono-Dabco-16-furazolidone provides a significant increase in antimicrobial activity (2 times against bacteria and 8 times against fungi) and reduces 2 times the dose of each of the components in combination formulation and causes <2% haemolysis of human red blood cells at the active dose.