Lipid Nanocarriers Impede Side Effects of Delivered Antimicrobial Peptide

Targeted delivery of pharmaceuticals with the help of nano-sized carriers is considered as a new paradigm in personalized medicine. It allows reducing the bulk amount of a drug while providing effective on-site concentration of acting agent. Antimicrobial decapeptide gramicidin S is effective against many bacteria, some fungi and viruses but is used only externally due to the hemolytic activity. It is assumed that for certain topically applied medicines encapsulation into liposomal or micellar delivery vehicles may alleviate their side-effects and the whole body burden. To test this hypothesis for antimicrobial drug gramicidin S (GrS) we have compared the effects of neat GrS and GrS encapsulated into spherical 100 nm liposomes on morphological and functional properties of human red blood cells (RBC). With the help of optical scattering and resistive pulse spectroscopy methods we have studied the effect of bare GS and GS-liposome complexes on shape, volume and electro osmotic properties of human red blood cells upon preliminary incubation. We accessed cell volume, critical dielectric breakdown voltage and membrane resistance to acid hemolysis. Idea appeared to be true partially - liposomal delivery of GrS may increase hemolytic concentration of antibiotic and widen therapeutic window for its system application, while high GrS concentrations (above 20 mM) are still harmful for RBC regardless of the way of drug administration - with nano-carriers or without.