Development of a high-level light-activated disinfectant for hard surfaces and medical devices.

BACKGROUND: Bacterial spores are an important consideration in healthcare decontamination, with cross-contamination highlighted as a major route of transmission due to their persistent nature. Their containment is extremely difficult due to the toxicity and cost of first-line sporicides. METHODS: Susceptibility of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli to phenothiazinium photosensitizers and cationic surfactants under white- or red-light irradiation was assessed by determination of minimum inhibitory concentrations, minimum bactericidal concentrations and time-kill assays. B. subtilis spore eradication was assessed via time-kill assays, with and without nutrient and non-nutrient germinant supplementation of photosensitizer, surfactant and photosensitizer-surfactant solutions in the presence and absence of light. RESULTS: Under red-light irradiation, >5-log10 colony-forming units/mL reduction of vegetative bacteria was achieved within 10 min with toluidine blue O (TBO) and methylene blue (MB). Cationic surfactant addition did not significantly enhance spore eradication by photosensitizers (P>0.05). However, addition of a nutrient germinant mixture to TBO achieved a 6-log10 reduction after 20 min of irradiation, while providing 1-2 log10 improvement in spore eradication for MB and pyronin Y. CONCLUSIONS: Light-activated photosensitizer solutions in the presence of surfactants and germination-promoting agents provide a highly effective method to eradicate dormant and vegetative bacteria. These solutions could provide a useful alternative to traditional chemical agents used for high-level decontamination and infection control within health care.

Optimization of singlet oxygen production from photosensitizer-incorporated, medically relevant hydrogels.

Photodynamic therapy and photodynamic antimicrobial chemotherapy are widely used, but despite this, the relationships between fluence, wavelength of irradiation and singlet oxygen (1 O2 ) production are poorly understood. To establish the relationships between these factors in medically relevant materials, the effect of fluence on 1 O2 production from a tetrakis(4-N-methylpyridyl)porphyrin (TMPyP)-incorporated 2-hydroxyethyl methacrylate: methyl methacrylate: methacrylic acid (HEMA: MMA:MAA) copolymer, a total energy of 50.48 J/cm2 , was applied at varying illumination power, and times. 1 O2 production was characterized using anthracene-9,10-dipropionic acid, disodium salt (ADPA) using a recently described method. Using two light sources, a white LED array and a white halogen source, the LED array was found to produce less 1 O2 than the halogen source when the same power (over 500 - 600 nm) and time conditions were applied. Importantly, it showed that the longest wavelength Q band (590 nm) is primarily responsible for 1 O2 generation, and that a linear relationship exists between increasing power and time and the production of singlet oxygen. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 320-326, 2017.

Photosensitisers - the progression from photodynamic therapy to anti-infective surfaces.

INTRODUCTION: The application of light as a stimulus in pharmaceutical systems and the associated ability to provide precise spatiotemporal control over location, wavelength and intensity, allowing ease of external control independent of environmental conditionals, has led to its increased use. Of particular note is the use of light with photosensitisers. AREAS COVERED: Photosensitisers are widely used in photodynamic therapy to cause a cidal effect towards cells on irradiation due to the generation of reactive oxygen species. These cidal effects have also been used to treat infectious diseases. The effects and benefits of photosensitisers in the treatment of such conditions are still being developed and further realised, with the design of novel delivery strategies. This review provides an overview of the realisation of the pharmaceutically relevant uses of photosensitisers, both in the context of current research and in terms of current clinical application, and looks to the future direction of research. EXPERT OPINION: Substantial advances have been and are being made in the use of photosensitisers. Of particular note are their antimicrobial applications, due to absence of resistance that is so frequently associated with conventional treatments. Their potency of action and the ability to immobilise to polymeric supports is opening a wide range of possibilities with great potential for use in healthcare infection prevention strategies.

Surface localisation of photosensitisers on intraocular lens biomaterials for prevention of infectious endophthalmitis and retinal protection.

Cataract surgery is one of the most commonly-practiced surgical procedures in Western medicine, and, while complications are rare, the most serious is infectious postoperative endophthalmitis. Bacteria may adhere to the implanted intraocular lens (IOL) and subsequent biofilm formation can lead to a chronic, difficult to treat infection. To date, no method to reduce the incidence of infectious endophthalmitis through bacterial elimination, while retaining optical transparency, has been reported. In this study we report a method to optimise the localisation of a cationic porphyrin at the surface of suitable acrylate copolymers, which is the first point of contact with potential pathogens. The porphyrin catalytically generates short-lived singlet oxygen, in the presence of visible light, which kills adherent bacteria indiscriminately. By restricting the photosensitiser to the surface of the biomaterial, reduction in optical transparency is minimised without affecting efficacy of singlet oxygen production. Hydrogel IOL biomaterials incorporating either methacrylic acid (MAA) or methyl methacrylate (MMA) co-monomers allow tuning of the hydrophobic and anionic properties to optimise the localisation of porphyrin. Physiochemical and antimicrobial properties of the materials have been characterised, giving candidate materials with self-generating, persistent anti-infective character against Gram-positive and Gram-negative organisms. Importantly, incorporation of porphyrin can also serve to protect the retina by filtering damaging shortwave visible light, due to the Soret absorption (λmax 430 nm).