Simultaneous Ultrasound-Assisted Hybrid Polyzwitterion/Antimicrobial Peptide Nanoparticles Synthesis and Deposition on Silicone Urinary Catheters for Prevention of Biofilm-Associated Infections

Abstract

Nosocomial infections caused by antibiotic-resistant bacteria are constantly growing healthcare threats, as they are the reason for the increased mortality, morbidity, and considerable financial burden due to the poor infection outcomes. Indwelling medical devices, such as urinary catheters, are frequently colonized by bacteria in the form of biofilms that cause dysfunction of the device and severe chronic infections. The current treatment strategies of such device-associated infections are impaired by the resistant pathogens but also by a risk of prompting the appearance of new antibiotic-resistant bacterial mechanisms. Herein, the one-step sonochemical synthesis of hybrid poly(sulfobetaine) methacrylate/Polymyxin B nanoparticles (pSBMA@PM NPs) coating was employed to engineer novel nanoenabled silicone catheters with improved antifouling, antibacterial, and antibiofilm efficiencies. The synergistic mode of action of nanohybridized zwitterionic polymer and antimicrobial peptide led to complete inhibition of the nonspecific protein adsorption and up to 97% reduction in Pseudomonas aeruginosa biofilm formation, in comparison with the pristine silicone. Additionally, the bactericidal activity in the hybrid coating reduced the free-floating and surface-attached bacterial growth by 8 logs, minimizing the probability for further P. aeruginosa spreading and host invasion. This coating was stable for up to 7 days under conditions simulating the real scenario of catheter usage and inhibited by 80% P. aeruginosa biofilms. For the same time of use, the pSBMA@PM NPs coating did not affect the metabolic activity and morphology of mammalian cells, demonstrating their capacity to control antibiotic-resistant biofilm-associated bacterial infections.