Photodynamic Therapy (Photoactivated Disinfection)

PHOTODYNAMIC THERAPY (PHOTOACTIVATED DISINFECTION)

The therapeutic effects of light have been known for thousands of years and the combination of light with various chemicals again dates back to ancient times. It was only at the beginning of the 20th century, however, that the scientific basis of this phenomenon began to be explored. The use of photosensitizing agents to kill microorganisms was first shown in 1900 and it was shortly after this that the term photodynamic therapy (PDT) was coined. This chapter only discusses the use of this technique for the killing of microorganisms, although it should be pointed out that PDT has also been used to treat tumours using a combination of photosensitizing porphyrin compounds and laser light.

The most common photosensitizers used for their antimicrobial effects are the thiazine dyes methylene blue and toluidine blue O (also known as tolonium chloride; Figure 27.1). Both of these molecules carry a positive charge and this enables them to interact with the negatively charged outer surfaces of bacteria. In particular, they accumulate at the cytoplasmic membrane and when activated cause lethal damage to that target site. It has been found that Gram-positive bacteria are more sensitive to PDT than Gram-negative bacteria, because of the different nature of their cell walls .

The light sources used in the recent past have been lasers which produce light of a defined waveband designed to match the peak excitation wavelength of the photosensitizer used. Lasers also have the advantage of being able to be passed through thin, flexible fibres for use in difficult-to-access areas. More recently, advances in the development of light-emitting diodes (LEDs), particularly in respect of their increasing power, has enabled these to be used under some circumstances in place of lasers with obvious benefits of safety and cost. Toluidine blue O has an absorbance peak of ±11 nm around the maximum and so is suitable for use in conjunction with these systems.

A detailed discussion of the mechanism of antimicrobial action of light-activated photosensitizers is outside the scope of this chapter and the reader is referred to Wainwright (1998) for further information. However, in brief, the photosensitizer which is adsorbed on to the bacterial cell will, when illuminated, give rise to the production of toxic singlet oxygen which is very short-lived but highly destructive. This singlet oxygen is present only when the photosensitizer is excited by light and does not persist once the light is extinguished. The toxic effect is confined to bacteria and the photosensitizer does not appear to have any adverse effects on normal tissue.

PDT is essentially a highly efficient disinfection process which is harmless to surrounding tissues. The limitations of the system are associated with the ability of both the dye and the light to penetrate the matrix in which the bacteria are located. The main use for the technology is therefore to treat localized, surface infections which are not particularly amenable to systemic therapy. It has been used extensively for infections in dentistry, particularly root canal infections, periodontitis and caries, and devices are commercially available for use in dental surgeries. Applications have also been found in dermatology, ophthalmology and ENT infections. It seems likely that the range of conditions appropriate for this technology will grow in the future, although the nature of the process is such that it will be a niche market treating localized, difficult-to-manage infections.