ABSTRACT
Amphiphilic antimicrobial polymers display activity against the outer bacterial cell membrane, triggering various physiological effects. We investigated the regulation of ion transport across the lipid bilayer to understand differences in biological activity for a series of amphiphilic polymethyloxazoline - polyethyleneimine copolymers. The results confirmed that the tested structures were able to increase the permeability of the lipid bilayer (LB) membrane or its rupture. Black lipid membrane (BLM) experiments show that the triggered conductance profile and its character is strongly correlated with the polymer structure and zeta potential. The polymer exhibiting the highest antimicrobial activity promotes ion transport by using a unique mechanism and step-like characteristics with well-defined discreet openings and closings. The molecule was incorporated into the membrane in a reproducible way, and the observed channel-like activity could be responsible for the antibacterial activity of this molecule.
Subject(s)
Anti-Bacterial Agents/chemistry , Lipid Bilayers/chemistry , Polymers/chemistry , Anti-Bacterial Agents/metabolism , Hydrogen-Ion Concentration , Ions/chemistry , Lipid Bilayers/metabolism , Magnesium/chemistry , Permeability , Polyethyleneimine/chemistry , Polymers/chemical synthesis , Polymers/metabolismABSTRACT
Polycations, mimicking activity of antibacterial peptides, belong to an important class of molecules investigated as a support or as an alternative to antibiotics. In this work, studies of modified linear amphiphilic statistical polymethyloxazoline (PMOX) and polyethyleneimine copolymers (PMOX_PEI) series are presented. Variation of PEI content in the structure results in controllable changes of polymeric aggregates zeta potential. The structure with the highest positive charge shows the best antimicrobial activity, well visible in tests against model Gram-positive and Gram-negative bacteria, fungi, and mycobacterium strains. The polymer toxicity is evaluated with MTT and hemolysis assay as a reference. Quartz crystal microbalance (QCM-D) is used to investigate interaction between polycations and a model lipid membrane. Polymer activity correlates well with molecular structure, showing that amphiphilic component is altering polymer behavior in contact with the lipid bilayer.
Subject(s)
Anti-Infective Agents/pharmacology , Lipid Bilayers/chemistry , Polyamines/pharmacology , Polyethyleneimine/pharmacology , Anti-Infective Agents/chemical synthesis , Antimicrobial Cationic Peptides/chemistry , Candida albicans/drug effects , Candida albicans/growth & development , Erythrocytes/drug effects , Escherichia coli/drug effects , Escherichia coli/growth & development , Hemolysis/drug effects , Humans , Microbial Sensitivity Tests , Molecular Mimicry , Molecular Structure , Mycobacterium avium/drug effects , Mycobacterium avium/growth & development , Mycobacterium bovis/drug effects , Mycobacterium bovis/growth & development , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/growth & development , Nontuberculous Mycobacteria/drug effects , Nontuberculous Mycobacteria/growth & development , Polyamines/chemical synthesis , Polyelectrolytes/chemistry , Polyethyleneimine/chemical synthesis , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development , Static Electricity , Structure-Activity RelationshipABSTRACT
Monodispersed spherical Ag-doped bioactive glass nanoparticles (Ag-BGNs) were synthesized by a modified Stöber method combined with surface modification. The surface modification was carried out at 25, 60, and 80 °C, respectively, to investigate the influence of processing temperature on particle properties. Energy-dispersive X-ray spectroscopy (EDS) results indicated that higher temperatures facilitate the incorporation of Ag. Hydroxyapatite (HA) formation on Ag-BGNs was detected upon immersion of the particles in simulated body fluid for 7 days, which indicated that Ag-BGNs maintained high bioactivity after surface modification. The conducted antibacterial assay confirmed that Ag-BGNs had an antibacterial effect on E. coli. The above results thereby suggest that surface modification is an effective way to incorporate Ag into BGNs and that the modified BGNs can remain monodispersed as well as exhibit bioactivity and antibacterial capability for biomedical applications.
