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REVIEW ARTICLE
Year : 2012  |  Volume : 3  |  Issue : 1  |  Page : 8-12

Photodynamics in antimicrobial periodontal therapy


Department of Periodontics, Vishnu Dental College, Bhimavaram, India

Date of Web Publication27-Sep-2012

Correspondence Address:
Sruthima NVS Gottumukkala
Department of Periodontics, Vishnu Dental College, Bhimavaram
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0976-6944.101669

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  Abstract 

Current dental practice has been emphasizing more on (1) early diagnosis and prevention of common oral diseases and (2) to conserve tooth structure as much as possible during restorative procedures. Thus atraumatic and non invasive treatment modalities have been the key thrust in dentistry today. Keeping in mind the tremendous potential of optical technology to provide high sensitive tissue information non-invasively, and the ability to induce localized and specific tissue changes, photodynamic therapy should be the foremost technology to embrace for advancement in dentistry. Although mechanical removal of the periodontal pathogens is the current gold standard of treatment, antibiotics are also known to be effective. However, development of resistance in the target organisms is a problem associated with the use of such drugs. The use of photoactivatable compounds or photosensitizers (PS) to cause photodestruction of oral bacteria has been demonstrated, indicating that photodynamic therapy (PDT) could be a useful alternative to mechanical means as well as antibiotics in eliminating periopathogenic bacteria. Keeping this in consideration this review mainly focuses on the application of photodynamic technology as antimicrobial agent in adjunct to the routine oral prophylaxis around the natural dentition as well as implant prosthesis.

Keywords: Implants, lasers in periodontitis, photodynamic antimicrobial chemotherapy, photodynamic therapy, photosensitizers


How to cite this article:
Gottumukkala SN, Mantena SR. Photodynamics in antimicrobial periodontal therapy. Indian J Oral Sci 2012;3:8-12

How to cite this URL:
Gottumukkala SN, Mantena SR. Photodynamics in antimicrobial periodontal therapy. Indian J Oral Sci [serial online] 2012 [cited 2017 Apr 27];3:8-12. Available from: http://www.indjos.com/text.asp?2012/3/1/8/101669


  Introduction Top


Periodontal disease is an infectious, inflammatory disease and its initiation and progression is significantly associated with overgrowth of certain pathogenic bacteria, liberation of bacterial toxins, and inflammatory response of the host. As more and more bacterial strains become resistant to antibiotics, the dental clinician is often faced with choosing alternatives to combat anaerobic bacteria that can lead to periodontal diseases. A primary related concern for the dental clinician is soft-tissue inflammation, bleeding, and suppuration, which can progress to fairly rapid bone loss. Elimination or adequate suppression of putative periodontopathic microorganisms in the subgingival microbiota is essential for periodontal healing. Antimicrobial treatment in periodontics ranges from mechanical debridement of tooth surfaces and home plaque removal, to local and systemic delivery of antimicrobial agents. Antimicrobial photodynamic therapy (aPDT) has emerged in the clinical field as a potential alternative to antibiotics to treat microbial infections. The aim of this review is to outline the clinical application and effects of photodynamic therapy in the management of periodontal and peri-implant infections.

Photodynamic therapy

Photodynamic therapy is defined as "the light-induced inactivation of cells, microorganisms, or molecules." [1] It is the combination of light and light sensitive agents (such as porphyrins) in an oxygen-rich environment. Photodynamic therapy is also called photoradiation therapy, phototherapy, or photochemotherapy. The term "photodynamic action" was first coined in the year 1904 by a photo biologist Hermann von tappeiner. John Toth acknowledged the "photodynamic chemical effect" of the therapy with early clinical argon dye lasers and renamed the therapy as "photodynamic therapy" (PDT).

Applications in dentistry

Photodynamic therapy has been used in (i) photodynamic diagnosis of malignant transformation of oral lesions, (ii) treatment of premalignant and malignant oral lesions, (iii) chemotherapy (PACT) of bacterial and fungal infections, (iv) prevention of alveolar ostitis and postextraction pain, (v) decontamination of implant surface and prevention and treatment of peri-implantitis, (vi) endodontic treatment.

Antimicrobial photodynamic therapy

Although mechanical removal of the periodontal pathogens is the current gold standard of treatment in periodontics, antibiotics are also known to be effective. The use of antibiotics to destroy microorganisms (MO) selectively represents one of the most revolutionary progresses made in scientific medicine, resulting in the treatment and sometimes complete eradication of earlier incurable diseases. [2],[3] However, bacteria have developed resistance mechanisms against antimicrobial drugs which were previously highly effective. Besides, bacteria replicate very rapidly and a mutation that helps a MO to survive in the presence of an antibiotic will quickly become predominant in the microbial population. The use of photoactivable compounds or photo sensitizers (PS) to cause photodestruction of oral bacteria has been demonstrated, indicating that photodynamic therapy (PDT) could be a useful alternative to mechanical means as well as antibiotics in eliminating periopathogenic bacteria. Antimicrobial photodynamic therapy (aPDT) represents a potential alternative methodology to inactivate microbial cells [4],[5],[6] and has already shown to be effective in vitro against bacteria, fungi, viruses, and protozoa. [7],[8],[9]

Photosensitizing agents

The majority of the sensitizers [Table 1] used clinically belong to dyes, the porphyrins, chlorins, and furocoumarins. The requirements of an optimal photosensitizer include photo-physical, chemical, and biological characteristics: should be able to produce singlet oxygen efficiently, should have a high absorption coefficient at the long wavelength region, should have no dark toxicity, should facilitate cross linking of all membranes, should be stable and easy to dissolve in injectable solvents, should be chemically pure.
Table 1: List of photosensitizers

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Photofrin (dihematoporphyrin ether) and other hematoporphyrin derivatives (HPDs) are referred to as first-generation photosensitizers. Photofrin is the most extensively studied and clinically used photosensitizer. Second-generation photosensitizers include 5-aminolevulinic acid (ALA), benzoporphyrin derivative (BPD), lutetium texaphyrin, temoporfin (mTHPC), tinethyletiopurpurin (SnET2), and talaporfin sodium (LS11). Foscan (mTHPC), the most potent second-generation photosensitizer, has been reported to be 100 times more active than Photofrin in animal studies. [10] These photosensitizers have a greater capability to generate singlet oxygen; however, they can cause significant pain during therapy, and, because of their high activity, even dim light (60 Watt bulb) can lead to severe skin photosensitivity. [11] The third agent, ALA, is an intrinsic photosensitizer that is converted in situ to a photosensitizer, protoporphyrin IX

Light source

PDT requires a source of light that activates the photosensitizer by exposure to low-power visible light at a specific wavelength. Human tissue transmits red light efficiently, and the longer activation wavelength of the photosensitizers results in deeper light penetration. High-power heat-generating lasers, such as carbon dioxide and Nd:YAG surgical lasers, have well-recognized destructive effects on bacteria, and data from in vivo studies indicate that risks of thermal injury can be substantial, although this varies markedly according to the wavelength used. In contrast, if low-power laser energy could be coupled into the bacterial cell wall, the energy required for destruction of bacteria would be quite small, and would pose little if any risk of injury to the pulp and periodontal ligament. Recently, nonlaser light sources, such as light-emitting diodes (LED), have also been applied in PDT. [12]

Mechanism of action

The aPDT approach is based on the photodynamic therapy concept that comprises the action of three components: a photosensitizing agent (PS), a light source of an appropriate wavelength (artificial light or sunlight), and oxygen. [2],[13],[14] Two oxidative mechanisms of photoinactivation (PI) are considered to be implicated in the inactivation of the target cells. The type I pathway involves electron/hydrogen atoms-transfer reactions from the PS triplet state with the participation of a substrate to produce radical ions while the type II pathway [Figure 1] involves energy transfer from that triplet state to molecular oxygen to produce singlet oxygen ( 1 O 2 ). [13] Both processes lead to highly toxic reactive oxygen species (ROS) such as 1 O 2 and free radicals, able to irreversibly alter vital components of cells resulting in oxidative lethal damage. [15],[16] The main advantages of aPDT are the nontarget specificity, the few side effects, prevention of the regrowth of the MO after treatment, and the lack of development of resistance mechanisms due to the mode of action and type of biochemical targets (multitarget process). The photodynamic activity produces damages mainly in the cytoplasmic membrane and in DNA. The damages to the cytoplasmic membrane can involve leakage of cellular contents or inactivation of membrane transport systems and enzymes. [17],[18]
Figure 1: Photodynamic action

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The photosensitivity of bacteria appears to be related to the charge of the sensitizer. In general, neutral or anionic photosensitizers bind efficiently to and inactivate Gram-positive bacteria, while they bind to some extent to the outer membrane of Gram-negative bacteria, but do not inactivate them after illumination. A relatively porous layer of peptidoglycan and lipoteichoic acid outside the cytoplasmic membrane of Gram-positive species allows the photosensitizer to diffuse into sensitive sites. The outer membrane of Gramnegative bacteria acts as a physical and functional barrier between the cell and its environment. The affinity of negatively charged photosensitizers for Gram-negative bacteria may be enhanced by linking the sensitizer to a cationic molecule (e.g., poly-L-lysine-chlorin e6), by the use of membrane-active agents (e.g., treatment with Tris-EDTA), or by conjugating the sensitizer with a monoclonal antibody that binds to cell-surface-specific antigens. [13]

Effect of aPDT on periodontopathic bacteria

The oral cavity is colonized by complex, relatively specific, and highly interrelated micro-organisms, including aerobic and anaerobic Gram-positive and Gram-negative bacteria, fungi, mycoplasma, protozoa, and viruses. The activity of photodynamic antimicrobial chemotherapy against homogenous and mixed Gram-positive/Gram-negative oral biofilms has been reported for a range of photosensitizers. [19],[20],[21],[22],[23] Activity of PACT against oral biofilm includes in vitro studies and few in vivo studies. All these studies found PDT to be effective in reducing bacterial load in the biofilm [Table 2]. However, Oliveira et al, could not find any statistical differences between PDT and scaling and root planning in patients with aggressive periodontitis. In vivo studies have also proved that PDT may be an effective alternative for control of bone loss in furcation areas in periodontitis. [34]
Table 2: Studies on the effect of photodynamic therapy on oral biofilm microorganisms

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Effect of aPDT on peri-implantitis

Peri-implantitis seems to occur in 5-10% of all implant cases. There is considerable debate, however, about whether bacterial contamination, occlusal overload, or some combination of the two is the primary factor responsible for inducing peri-implantitis. "Whatever its genesis," it was found that poor oral hygiene accelerates the process. Laser treatment is best combined with surgical opening of the implant site for cleaning and disinfecting the local defect. In this way, photodynamic therapy can be used successfully to decontaminate the implant surface. [33],[35]


  Conclusion Top


While antibiotics can effectively inhibit or eliminate the growth of bacteria, the complexities associated with patient compliance, with dosage and use, resistant strains of bacteria, and serious side effects can lead the dental practitioner to seek more attractive protocols for combating such infection. Because of the limitations associated with these more conventional means of antimicrobial treatment, it can be explained that photodynamic therapy is often an attractive alternative for the dental clinician.

 
  References Top

1.Antimicrobial photodynamic therapy. Grieskirchen, Austria: HELBO Photodynamic Systems GmbH and Co KG: ©2004. Available from http://www.helbo.de/en/apt_index. php. [Last accessed on 2004 Dec 29].  Back to cited text no. 1
    
2.Jori G, Brown SB. Photosensitized inactivation of microorganisms. Photochem Photobiol Sci 2004;3:403-5.  Back to cited text no. 2
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3.Tunger O, Dinc G, Ozbakkaloglu B, Atman C, Algun U. Evaluation of rational antibiotic use. Int J Antimicrob Agents 2000;15:131-5.  Back to cited text no. 3
    
4.Caminos DA, Spesia MB, Pons P, Durantini EN. Mechanisms of Escherichia coli photodynamic inactivation by an amphiphilic tricationic porphyrin and 5,10,15,20-tetra(4-N,N,Ntrimethylammoniumphenyl) porphyrin. Photochem Photobiol Sci 2008;7:1071-8.  Back to cited text no. 4
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7.Alves E, Costa L, Carvalho C, Tome J, Faustino M, Neves M, et al. Charge effect on the photoinactivation of Gram-negative and Gram-positive bacteria by cationic meso-substituted porphyrins. BMC Microbiol 2009;9:70-83.  Back to cited text no. 7
    
8.Alves E, Carvalho CM, Tomé JP, Faustino MA, Neves M, Tomé AC, et al. Photodynamic inactivation of recombinant bioluminescent Escherichia coli by cationic porphyrins under artificial and solar irradiation. J Ind Microbiol Biotechnol 2008;35:1447-54.  Back to cited text no. 8
    
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14.Jori G, Fabris C, Soncin M, Ferro S, Coppellotti O, Dei D, Fantetti L, et al. Photodynamic therapy in the treatment of microbial infections: Basic principles and perspective applications. Lasers Surg Med 2006;38:468-81.  Back to cited text no. 14
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24.Gueorgieva T, Dimitrov S, Dogandhiyska V, Kalchinov V, Belcheva M, Mantareva V, et al. Susceptibility of saureus to methylene blue haematoporphyrin, phtalocyanines photodynamic effects. Journal of IMAB (international medical association Bulgaria) 2010;16:51  Back to cited text no. 24
    
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29.Maisch T, Baier J, Franz B, Maier M, Landthaler M, Szeimies RM, et al. The role of singlet oxygen and oxygen concentration in photodynamic inactivation of bacteria. Proc Natl Acad Sci U S A 2007;104:7223-8.  Back to cited text no. 29
    
30.Williams JA, Pearson GJ, Colles MJ. Antibacterial action of photoactivated disinfection {PAD} used on endodontic bacteria in planktonic suspension and in artificial and human root canals. J Dent 2006;34:363-71.  Back to cited text no. 30
    
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32.Soukos NS, Mulholland SE, Socransky SS, Doukas AG. Photodestruction of human dental plaque bacteria: enhancement of the photodynamic effect by photomechanical waves in an oral biofilm model. Lasers Surg Med 2003;33:161-8.  Back to cited text no. 32
    
33.Dortbudak O, Haas R, Bernhart T. Lethal photosensitization for decontamination of implant surfaces in the treatment of peri-implantitis. Clin Oral Implants Res 2001;12:104-8.  Back to cited text no. 33
    
34.de Almeida JM, Theodoro LH, Bosco AF, Nagata MJ, Oshiiwa M, Garcia VG. In Vivo Effect of Photodynamic Therapy on Periodontal Bone Loss in Dental Furcations. J Periodontol 2008;79:1081-8.  Back to cited text no. 34
    
35.Shibli JA, Martins MC, Theodoro LH. Lethal photosensitization in microbiological treatment of ligature-induced periimplantitis: A preliminary study in dogs. J Oral Sci 2003;45:17-23.  Back to cited text no. 35
    


    Figures

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    Tables

  [Table 1], [Table 2]


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