A synergistic anti-bacterial effect with cold atmospheric plasma (cap) and silver antibiotic nanoparticles

摘要

Introduction: As we all know, bacteria play a central role in the development of infections, and eradicating specific pathogenic bacteria without an adverse effect on normal mammalian cells still remains a major challenge in medicine today. Traditional anti-microbial applications involve antibiotics, UV photons, and/or nanoparticles, but they all have shortcomings such as the development of antibiotic-resistant bacteria and a low efficacy for killing specific bacteria. Cold-atmospheric plasma (CAP) is emphasized here as a novel effective alternative to traditional antibiotics for non-systemic infections due to the role plasma treatment may play against a range of microorganisms, even including antibiotic-resistant biofilm-forming strains and spores, with minimal damage to surrounding cells El. Materials and Methods: Here, methicillin (as a model antibiotic) and silver nanoparticles were encapsulated inside polymersomes by a self-assembly method. The encapsulated polymersomes were characterized for shape, chemistry, drug release and ultimately were then exposed to multidrug-resistant Escherichia coli at log phase prepared in fresh medium diluted to an optical density equivalent to 5~*106 CFU/ml. Aliquots from standardized bacterial suspension were additionally exposed to the cold plasma plume for various treatment times. After plasma exposure, each sample was transferred to fresh medium and a spectrophotometer was used to determine the speed of bacteria proliferation and shape of bacterial growth curves. All experiments were repeated in triplicate at least three times. Results and Discussion: This study showed that it is possible to overcome antibiotic-resistance through the presently combined delivery of silver nanoparticles and methicillin with the application of CAP. The antibacterial effect improved when polymersome concentration increased. The combined treatment of polymersomes and CAP resulted in a synergistic activity sufficient to delay or completely inhibit the growth of multidrug resistance bacteria. Under same concentration of polymersomes, bacterial growth was further delayed with CAP post-treatment when compared with non-CAP treatment. This was especially true for the all polymersome concentration where bacterial growth was delayed after 24 hrs, the longest time point studied here. Conclusions: The present study demonstrated that antibiotics and silver nanoparticles can be successfully encapsulated into polymersomes. Impressively, these polymersome nanoparticles combined with CPA therapy can significantly delay or completely inhibit the growth of multi-drug resistant bacteria.