Advances in photodynamic therapy in periodontics

Introduction:

Although a lot of research has been done onphotodynamic therapy, it is still one of the most popular research topics presently. The photodynamic therapy works on the principle of photon energy. When a photon of light is absorbed by a molecule of the photosensitizer in its ground singlet state (S), it is excited to the singlet state (S*) after it receives the energy of the photon. The lifetime of the S* state is very small (in nano second range) and it rapidly releases energy in the form of light (fluorescence) or by internal conversion with energy lost as heat. So, what is the link between a photosensitizer and microbial killing? Photosensitizer is absorbed by microorganisms and following exposure to light of the appropriate wavelength, it becomes activated to an excited state.  Then it transfers its energy from light to molecular oxygen to generate singlet oxygen and free radicals that are cytotoxic to the bacterial cells. The photodynamic therapy also has stimulating effects on fibroblasts, hence helpful in wound healing. Photosensitizer molecules have been attached to antibodies directed against various periodontal pathogens.

Photosensitizers:

Most of the photosensitizers used basically have tetrapyrrole nucleus. These include porphyrins, chlorins, bacteriochlorins and phthalocyanines. This tetrapyrrole ring structure is named porphin and derivatives of porphins are named porphyrins.

Following photosensitizers are presently available for clinical use

  1. mesotetra-hydroxyphenyl-chlorin (mTHPC, temoporfin,Foscan®; Biolitec Pharma Ltd., Dublin, Ireland),
  2. benzoporphyrin derivative monoacid A (BPD-MA, Visudyne®; QLT Inc., Vancouver, Canada and Novartis Opthalmics, Bulach, Switzerland)
  3. 5- or daminolevulinic acid (ALA, Levulan®; DUSA Pharmaceuticals Inc., Wilmington, MA, USA)
  4. Methyl ester of ALA (Metvix®; Photocure ASA, Oslo, Norway)

Current research:

Photodynamic therapy has been used for the treatment of cancer, age-related macular degeneration, actinic keratosis and Barrett’s esophagus. In dentistry photodynamic therapy has been used in following

  • Bactericidal effects on cariogenic bacteria, either in the planktonic phase or in biofilm1-6.
  • Bactericidal effects on periodontal pathogens to eliminate subgingival species and treat periodontitis7-10.
  • Photodynamic therapy has been employed in recent years as root canal disinfection procedure11-14.
  • Photodynamic therapy has been used to treat oral candidiasis15-17.
  • Antibodies conjugated with photosensitizers have been used on periodontal pathogens18-21.
  • Photodynamic therapy has been used to stimulate fibroblast growth in healing periodontal lesions.

A study can be designed on any of above stated points after going through complete details of research work already done. The major requirements for the study include the photosensetizer and diode laser.

References:

  1. Bevilacqua IM, Nicolau RA, Khouri S, Brugnera A Jr, Teodoro GR, Zangaro RA, Pacheco MT. The impact of photodynamic therapy on the viability of Streptococcus mutans in a planktonic culture. Photomed Laser Surg 2007: 25: 513–518.
  2. Burns T, Wilson M, Pearson GJ. Sensitisation of cariogenic bacteria to killing by light from a helium-neon laser. J Med Microbiol 1993: 38: 401–405.
  3. Burns T, Wilson M, Pearson GJ. Killing of cariogenic bacteria by light from a gallium aluminium arsenide diode laser. J Dent 1994: 22: 273–278.
  4. Williams JA, Pearson GJ, Colles MJ, Wilson M. The effect of variable energy input from a novel light source on the photoactivated bactericidal action of toluidine blue O on Streptococcus mutans. Caries Res 2003: 37: 190–193.
  5. Zanin IC, Goncalves RB, Junior AB, Hope CK, Pratten J. Susceptibility of Streptococcus mutans biofilms to photodynamic therapy: an in vitro study. J Antimicrob Chemother 2005: 56: 324–330.
  6. Zanin IC, Lobo MM, Rodrigues LK, Pimenta LA, Hofling JF, Goncalves RB. Photosensitization of in vitro biofilms by toluidine blue O combined with a light-emitting diode. Eur J Oral Sci 2006: 114: 64–69.
  7. Bhatti M, MacRobert A, Henderson B, Wilson M. Exposure of Porphyromonas gingivalis to red light in the presence of the light-activated antimicrobial agent toluidine blue decreases membrane fluidity. Curr Microbiol 2002: 45: 118–122.
  8. Bhatti M, MacRobert A, Meghji S, Henderson B, Wilson M. Effect of dosimetric and physiological factors on the lethal photosensitization of Porphyromonas gingivalis in vitro. Photochem Photobiol 1997: 65: 1026–1031.
  9. Dobson J, Wilson M. Sensitization of oral bacteria in biofilms to killing by light from a low-power laser. Arch Oral Biol 1992: 37: 883–887
  10. Wood S, Nattress B, Kirkham J, Shore R, Brookes S, Griffiths J, Robinson C. An in vitro study of the use of photodynamic therapy for the treatment of natural oral plaque biofilms formed in vivo. J Photochem Photobiol B 1999: 50: 1–7.
  11. Fimple JL, Fontana CR, Foschi F, Ruggiero K, Song X, Pagonis TC, Tanner AC, Kent R, Doukas AG, Stashenko PP, Soukos NS. Photodynamic treatment of endodontic polymicrobial infection in vitro. J Endod 2008: 34: 728–734.
  12. Foschi F, Fontana CR, Ruggiero K, Riahi R, Vera A, Doukas AG, Pagonis TC, Kent R, Stashenko PP, Soukos NS. Photodynamic inactivation of Enterococcus faecalis in dental root canals in vitro. Lasers Surg Med 2007: 39: 782–787.
  13. Garcez AS, Ribeiro MS, Tegos GP, Nunez SC, Jorge AO, Hamblin MR. Antimicrobial photodynamic therapy combined with conventional endodontic treatment to eliminate root canal biofilm infection. Lasers Surg Med 2007: 39: 59–66.
  14. George S, Kishen A. Advanced noninvasive light-activated disinfection: assessment of cytotoxicity on fibroblast versus antimicrobial activity against Enterococcus faecalis. J Endod 2007: 33: 599–602.
  15. Bliss JM, Bigelow CE, Foster TH, Haidaris CG. Susceptibility of Candida species to photodynamic effects of photofrin. Antimicrob Agents Chemother 2004: 48: 2000–2006.
  16. Cormick MP, Alvarez MG, Rovera M, Durantini EN. Photodynamic inactivation of Candida albicans sensitized by tri- and tetra-cationic porphyrin derivatives. Eur J Med Chem 2009: 44: 1592–1599.
  17. Giroldo LM, Felipe MP, de Oliveira MA, Munin E, Alves LP, Costa MS. Photodynamic antimicrobial chemotherapy (PACT) with methylene blue increases membrane permeability in Candida albicans. Lasers Med Sci 2009: 24: 109–112.
  18. Bhatti M, MacRobert A, Henderson B, Shepherd P, Cridland J, Wilson M. Antibody-targeted lethal photosensitization of Porphyromonas gingivalis. Antimicrob Agents Chemother 2000: 44: 2615–2618.
  19. Embleton ML, Nair SP, Cookson BD, Wilson M. Selective lethal photosensitization of methicillin-resistant Staphylococcus aureus using an IgG-tin (IV) chlorin e6 conjugate. J Antimicrob Chemother 2002: 50: 857–864.
  20. Embleton ML, Nair SP, Heywood W, Menon DC, Cookson BD, Wilson M. Development of a novel targeting system for lethal photosensitization of antibiotic-resistant strains of Staphylococcus aureus. Antimicrob Agents Chemother 2005: 49: 3690–3696.
  21. Hope CK, Packer S, Wilson M, Nair SP. The inability of a bacteriophage to infect Staphylococcus aureus does not prevent it from specifically delivering a photosensitizer to the bacterium enabling its lethal photosensitization. J Antimicrob Chemother 2009: 64: 59–61.

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