Bactericidal and hemolytic properties of mixed LL-37/surfactant systems

The interaction between acyl chain homologues (C10 and C12) of n-acyl β-D-maltoside and the antimicrobial peptide LL-37 (LLGDFFRK- SKEKIGKEFKRIVQRIKDFLRNLVPRTES) was investigated. Emphasis was placed on peptide-micelle complexation and its consequences for peptide proteolytic stability, as well as bactericidal and hemolytic effects of the mixed systems. From circular dichroism and liposome leakage experiments, it was found that LL-37 interacts with both surfactants investigated, and that this reduces the effective free peptide concentration. Analogously, LL-37 displayed increased proteolytic stability towards Pseudomonas aeruginosa elastase in surfactant solution. Despite this, conditions can be found at which the bactericidal effect of mixed peptide-surfactant systems is comparable to that of free LL-37. However, also a number of challenges to this type of antimicrobial peptide (AMP) carrier system were identified, notably related to reduction of bactericidal effect for some systems, and occurrence of hemolysis for mixed peptide-surfactant systems displaying advantageous bactericidal effects. Any use of such AMP carrier systems will therefore have to be carefully optimized in order to retain bactericidal activity and minimize toxicity.