Antimicrobial photodynamic therapy as a new approach for the treatment of vulvovaginal candidiasis: preliminary results
In this work, we present the efficacy of photodynamic therapy against yeast cells in an animal model. We tested two photosensitizers, methylene blue and protoporphyrin IX. Thirty-seven female BALB-c mice with a body mass of 20–25 g were used. To achieve persistent vaginitis, estrus was induced by subcutaneous injection of 0.1 mg/mL estradiol valerate applied weekly. Three days after pseudo-estrus, intravaginal inoculation with Candida albicans was performed. Mice were anesthetized with ketamine (80 mg/kg) and xylazine (10 mg/kg) by intraperitoneal injection before inoculation, and antimicrobial photodynamic therapy (aPDT) was performed 5 days after fungal inoculation. Two photosensitizers were tested, methylene blue (MB; 100 μM) and protoporphyrin IX (PpNetNI; 10 μM). Two custom-made LEDs emitting light at 660 and 630 nm at approximately 800 mW each were used for irradiation. The aPDT treatment reduced the fungal colony-forming units (CFUs) by one order of magnitude for the MB (p = 0.020) and PpNetNI (p = 0.018) photosensitizers. Seven days after the treatment, there were significantly fewer CFUs compared to the control group (p = 0.041 and p = 0.035 for MB and PpNetNI, respectively), but this was not increased compared to the initial number immediately after aPDT. Using aPDT as a therapeutic option to decrease fungal infection in a vaginal candidiasis model resulted in a significant reduction in the C. albicans population. Both photosensitizers were effective for preventing reinfection within 7 days. The aPDT also had no effect on the vaginal mucosa at the ultrastructural level. In addition to the fungicide effect, we observed reduced swelling and lack of the formation of abscesses, microabscesses coating the cornified epithelial layer, and the accumulation of neutrophils in the submucosa.
KeywordsLaser Photobiomodulation Antimicrobial photodynamic therapy Candida Vulvovaginal candidiasis Candidiasis treatment
The work was partially funded by the São Paulo Research Foundation (FAPESP) grant 08/57721-3.
Compliance with ethical standards
The Ethics Committee of Universidade Nove de Julho (protocol number 00025/2013) approved this work.
Conflict of interest
The authors declare that they have no conflicts of interest.
The Ethics Committee of Universidade Nove de Julho (protocol number 00025/2013) approved this study.
This work involved an animal study; therefore, obtaining informed consent was not necessary.
- 1.Gonçalves B, Ferreira C, Alves CT, Henriques M, Azeredo J, Silva S (2015) vulvovaginal candidiasis: epidemiology, microbiology and risk factors. Crit Rev Microbiol 21:1–23Google Scholar
- 7.Gallemore RP, Boyer DS (2006) PDT or anti-VEGF for AMD treatment. Rev of OphthalmologyGoogle Scholar
- 12.Alvarenga LH, Prates RA, Yoshimura TM, Kato IT, Suzuki LC, Ribeiro MS, Ferreira LR, Pereira SA, Martinez EF, Saba-Chujfi E (2015) Aggregatibacter actinomycetemcomitans biofilm can be inactivated by methylene blue-mediated photodynamic therapy. Photodiagn Photodyn Ther 12:131–135CrossRefGoogle Scholar
- 17.Ferreira LR, Sousa AS, Alvarenga LH, Deana AM, de Santi MEOS, Kato IT, Leal CRL, Ribeiro MS, Prates RA (2016) Antimicrobial photodynamic therapy on Candida albicans pre-treated by fluconazole delayed yeast inactivation. Photodiagn Photodyn Ther 7:15–25Google Scholar
- 20.Rineh A, Dolla NK, Ball AR, Magana M, Bremner JB, Hamblin MR, Tegos GP, Kelso MJ (2017) Attaching the NorA efflux pump inhibitor INF55 to methylene blue enhances antimicrobial photodynamic inactivation of methicillin-resistant Staphylococcus aureus in vitro and in vivo. ACS Infect Dis 3:756–766CrossRefGoogle Scholar
- 22.G.P. Tegos; K. Masago, F. Aziz, A. Higginbotham, F.R. Stermitz, M.R Hamblin (2008) Antimicrob Agents Chemother. 52(9):3202–9Google Scholar