Positive results from initial in vitro studies suggest that photodynamic therapy (PDT) holds promise for overcoming biofilm-related microbial resistance, says Thomas S. Mang, Ph.D.
Buffalo, N.Y. - Positive results from initial in vitro studies suggest that photodynamic therapy (PDT) holds promise for overcoming biofilm-related microbial resistance, says Thomas S. Mang, Ph.D.
Dr. Mang has been investigating PDT disinfection of oral biofilm in research conducted at the School of Dental Medicine, University at Buffalo, N.Y., but he was previously involved with the development of PDT for treatment of cutaneous and other cancers while at Roswell Park Cancer Institute.
Last year, Dr. Mang reported results from studies showing that in planktonic cultures, strains of Streptococcus mutans as well as various Candida species, including fluconazole and amphotericin B resistant isolates, were extremely sensitive to PDT performed using porfimer sodium (Photofrin, Pinnacle Biologics) as the photosensitizer and a 630 nm laser for activation. Testing in biofilm models showed PDT was effective in significantly reducing the viability of these same microbes as assessed by measurement of metabolic activity and using electron microscopy.
Initial testing of the susceptibility of antifungal resistant Candida species to PDT was performed in normal and planktonic cultures using clinical isolates obtained from patients with AIDS. The test organisms included strains of C. albicans, C. glabrata and C. krusei. The experimental methods included testing of a range of exposure parameters, and strikingly, efficacy was achieved using relatively short incubation times and low levels of laser light.
"Whereas a 24- to 48-hour incubation period is needed after injection of the photosensitizer when performing PDT for squamous cell or basal cell carcinoma, we found that drug uptake by the bacteria and yeast was very rapid, so that efficacy was achieved with incubation times as short as five minutes and up to one hour as a maximum. Furthermore, the effective light dose for reducing colonies in planktonic cultures was as low as 4.5 J/cm2 . This is equivalent to a 30-second irradiation time and is less than 10 percent of the exposure needed in treating the dermatologic cancers," says Dr. Mang, associate professor and director of research, Oral and Maxillofacial Surgery, School of Dental Medicine, University at Buffalo.
"These parameters would confer some significant clinical advantages. The short incubation time makes the treatment more convenient and results in a very selective therapeutic ratio for the photosensitizer between the microorganisms and normal tissue to improve treatment safety, while the low light doses needed allow for relatively short treatment times that would also enhance clinical acceptance," he adds.
The oral biofilm experiments were done in one model in which the methodology for growing the material increases the biofilm's strength and also using a flow cell technique that attempts to simulate the unique environmental conditions of the oral cavity. Even using these models that aim to create challenging scenarios for achieving disinfection, PDT was highly effective in reducing microbial viability.
In ongoing research, Dr. Mang will be testing the efficacy of PDT in other biofilm models and in vivo in animals, and they are also evaluating the efficacy of PDT for destroying the biofilm, which is also considered an important part of the equation in the clinical efficacy of the intervention.
Disclosures: Porfimer sodium was supplied for the research by Axcan Pharma. Dr. Mang reports no financial interests in that company.