Nitric Oxide-Releasing Polymer-Based Systems for Antibiofilm Applications

Bacterial cells are well known to embed within self-produced extracellular substance known as biofilms which protect them from most antibacterial agents. Biofilm-related infections not only cause human pain but also place a substantial economic burden on society. One approach to overcome this global challenge involves the use of the nitric oxide (NO) molecule. However, practical applications of NO donors have been hindered by their poor stability and lack of localized delivery. The utilization of polymers in nitric oxide delivery has been shown to be a promising strategy to surmount these weaknesses. This work aimed to explore polymer-based platforms for NO delivery. Firstly, synthesis of nanoparticles with two morphologies for the delivery of NO were explored. The spherical and cylindrical nanoparticles were prepared using Photo-initiated Polymerization Induced Self-Assembly and employed to encapsulate N-diazeniumdiolate in their cores. The resulting NO-releasing nanoparticles demonstrated excellent antibacterial activity at very low concentrations. Additionally, the NO release rate and biofilm dispersal were found to strongly depend on the nanoparticle morphology. In the second approach, the versatile adhesion feature of polydopamine (pDA) was used to prepare NO-releasing coatings that could prevent the formation of biofilm. A facile coating process was implemented to design a coating that possessed low-fouling properties (conferred by polyethylene glycol) and NO-releasing capabilities. The novel feature of this work was the applicability of this facile technology for a broad range of surfaces, including polymer films and inorganic surfaces (glass). The introduction of both functionalities in pDA film prevented the formation of P. aeruginosa biofilms, including a multidrug-resistant strain, on substrates and killed 99.9% of any adhered bacteria biofilm cells. The third approach included the development of an antibiofilm coating that possessed S-nitrosothiol NO donors for biofilm prevention applications. Cell culture dishes with 4 different film thicknesses were coated via plasma polymerization (PP) using a thiol monomer. The thiol functionality on the substrates was converted to S-nitrosothiol NO precursors. The plasma-modified surfaces showed 81% inhibition of P. aeruginosa bacterial attachment to the surface after 24 h exposure to the bacterial solution and presented a potential viable strategy to inhibit bacterial biofilm formation