Polymeric systems for antimicrobial photodynamic therapy of bacterial wound infections

Antimicrobial photodynamic therapy (aPDT) is a promising alternative to conventional antibiotics for treating and preventing microbial infections, owing to its broad-spectrum activity and low potential for resistance development. For application in future advanced wound dressings, photosensitisers (PSs) must be immobilised or encapsulated to maintain a high local concentration at the site of infection. This Thesis investigates the incorporation of the FDA-approved xanthene dye Phloxine B (PhB) as a PS for aPDT into polymer-based delivery systems. The first part of this work examines the fundamental photophysical behaviour of PhB, including its absorption and emission, pH-dependence, 1O2 generation and photostability. The aPDT activity of PhB was systematically evaluated against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Pseudomonas aeruginosa (P. aeruginosa), common pathogens found in wound infections, establishing its efficacy as an aPDT agent. Building on these findings, the second part of this Thesis focuses on the synthesis and characterisation of amphiphilic poly(ethylene glycol)-block-polyester (PEG-b-polyester) copolymers and their self-assembly into nanoscale assemblies for PhB encapsulation. Copolymers with varying hydrophobic block lengths formed assemblies with diameters ranging from 50-200 nm. As a water-soluble PS, PhB was encapsulated into polymeric vesicles ~200 nm in diameter, achieving dye concentrations >30 µM in the vesicle suspensions. Encapsulated PhB retained its aPDT activity, successfully eradicating both S. aureus and P. aeruginosa after 15 min of green light irradiation. The timescales of the antibacterial studies suggested at most limited internalisation of PhB, motivating the development of immobilised PhB-chitosan (CS) films. The final part of the Thesis therefore explores these PhB-CS films as aPDT surfaces, demonstrating effective inactivation of both planktonic and biofilm-associated bacteria upon light activation. Overall, this Thesis advances the integration of PhB into functional polymeric materials for application in advanced wound dressings.