Antimicrobial photodynamic therapy using organic light emitting diodes : rapid optimisation to advance to clinical application

Skin and soft tissue infections represent a major cause of patient’s ill health and treatment seeking behaviour at all stages of life. Bacteria are the major cause of skin infections in humans. Antimicrobial resistance is on the rise in community associated infections, especially in vulnerable patients such as those with Diabetic Foot Ulcers (DFU). This reinforces the necessity for new therapies to be developed. Antimicrobial photodynamic therapy (aPDT) is a promising new approach for skin and soft tissue infections that uses atmospheric oxygen, photosensitisers and a light source. Advancing this field of research and clinical application includes development of new, small and affordable light sources; Organic Light Emitting Diodes (OLEDs) are electroluminescent devices with these specific characteristics; therefore, a promising light source for use with PDT. The antimicrobial application of PDT is advantageous due to the non-selective oxidative damage on bacterial cellular structures, acting on multiple targets simultaneously. Different photosensitisers have varying degrees of effectiveness in different clinical scenarios. The Scattered Light Integrating Collector, a technology that optically measures bacterial growth in real time, was adapted for screening methylene blue (MB), new methylene blue (NMB) and di-methyl-methylene blue (DMMB) for use in OLED-aPDT. This thesis shows the value of SLIC for optimising OLED-aPDT in vitro, providing results in 2 hours and showing the efficaciousness of different photosensitisers against a range of bacteria. NMB and DMMB, which are derivatives of MB, showed better bacterial inhibition, with DMMB effectively sterilising Staphylococcus aureus cultures. OLED-aPDT using methylene blue was also investigated clinically as an adjuvant treatment for DFU. The use of OLED-aPDT promoted healing in 8 DFUs treated, improving wound closure and decreasing bacterial load, whilst being well-tolerated by the participants treated. OLED-aPDT could represent a major advance for treatment of skin and soft tissue infections using portable, low-cost devices.