Indian Journal of Dental Research

SHORT COMMUNICATION
Year
: 2015  |  Volume : 26  |  Issue : 4  |  Page : 439--442

Scope of photodynamic therapy in periodontics


Vivek Kumar1, Jolly Sinha2, Neelu Verma2, Kamal Nayan3, CS Saimbi2, Amitandra K Tripathi2,  
1 Department of Periodontology, Mithila Minority Dental College and Hospital, Darbhanga, Bihar, India
2 Department of Periodontology, Career Postgraduate Institute of Dental Sciences and Hospital, Lucknow, Uttar Pradesh, India
3 Department of Prosthodontics, Mithila Minority Dental College and Hospital, Darbhanga, Bihar, India

Correspondence Address:
Vivek Kumar
Department of Periodontology, Mithila Minority Dental College and Hospital, Darbhanga, Bihar
India

Abstract

Periodontal disease results from inflammation of the supporting structure of the teeth and in response to chronic infection caused by various periodontopathic bacteria. The mechanical removal of this biofilm and adjunctive use of antibacterial disinfectants and antibiotics have been the conventional methods of periodontal therapy. However, the removal of plaque and the reduction in the number of infectious organisms can be impaired in sites with difficult access. Photodynamic therapy (PDT) is a powerful laser-initiated photochemical reaction, involving the use of a photoactive dye (photosensitizer) activated by light of a specific wavelength in the presence of oxygen. Application of PDT in periodontics such as pocket debridement, gingivitis, and aggressive periodontitis continue to evolve into a mature clinical treatment modality and is considered as a promising novel approach for eradicating pathogenic bacteria in periodontitis.



How to cite this article:
Kumar V, Sinha J, Verma N, Nayan K, Saimbi C S, Tripathi AK. Scope of photodynamic therapy in periodontics.Indian J Dent Res 2015;26:439-442


How to cite this URL:
Kumar V, Sinha J, Verma N, Nayan K, Saimbi C S, Tripathi AK. Scope of photodynamic therapy in periodontics. Indian J Dent Res [serial online] 2015 [cited 2020 Mar 28 ];26:439-442
Available from: http://www.ijdr.in/text.asp?2015/26/4/439/167636


Full Text



Periodontal disease caused by dental plaque is characterized by the clinical signs of inflammation and loss of periodontal tissue support. The removal of the biofilm and adjunctive use of antibacterial disinfectants and antibiotics have been the conventional methods of periodontal therapy.[1] The current concepts are based on mechanical scaling and root planning to remove bacterial deposits, calculus, and cementum contaminated by bacteria and endotoxins.[2],[3] However, removal of plaque and the reduction of the number of infectious cells can be impaired in sites with difficult access. The possibility of development of resistance to antibiotics by the target organism has led to the development of a new antimicrobial concept with fewer complications.[4],[5]

Photodynamic therapy (PDT) has emerged in recent years as a noninvasive therapeutic modality for the treatment of various infections by bacteria, fungi, and viruses.[6] It involves the use of low power lasers with appropriate wavelength to kill microorganisms treated with a photosensitizer drug.[7] PDT could be a useful adjunct to mechanical, as well as antibiotics, in eliminating periopathogenic bacteria. This therapy is defined as an oxygen-dependent photochemical reaction that occurs upon light-mediated activation of a photosensitizing compound leading to the generation of cytotoxic reactive oxygen species; predominantly singlet oxygen.[8]

Applications of PDT in dentistry are growing rapidly. They are also used in the treatment of oral cancer, bacterial, and fungal infections, and in the photodynamic diagnosis of the malignant transformation of oral lesions.[9] This review is aimed to discuss the role of PDT in periodontal therapy.

 Historical Perspective of Photodynamic Therapy



The concept of treatment with light and photoactive compounds can be traced back over 6000 years to the ancient Egyptians who used light-sensitive substances (psoralens) by crushing leaves of plants related to parsley with sunlight to treat sunburns. Reference to the use of a plant extract for the restoration of skin pigmentation was made in 1400 BC, and phototoxic effects of psoralens were described in 1250 AD.[10] The use of contemporary PDT was first reported by the Danish physician, Niels Finsen. He successfully demonstrated PDT by employing heat-filtered light from a carbon - arc lamp (The Finsen Lamp) in the treatment of a tubercular condition of the skin known as lupus vulgaris.[11] The concept of cell death induced by the interaction of light and chemicals was first reported by Raab,[12] a medical student working with Prof. Herman Von Tappeiner in Munich. Subsequent work in the laboratory of Von Tappeiner coined the term “Photodynamic action” and showed that oxygen was essential.[13] Much later, Dougherty et al. at Roswell Park Cancer Institute, Buffalo, New York, clinically tested PDT.[14] Wilson proved the effect of cyanide photosensitizer on Gram-negative and Gram-positive species. Thereafter, in the recent past many combinations of lasers and photosensitizers were tried and different parameters with varying successes.[15]

Principles of photodynamic therapy

PDT is based on the principle that a photoactivable substance (the photosensitizer) binds to the target cell and can be activated by light of a suitable wavelength. During this process, free radicals are formed (among them singlet oxygen), which then produce an effect that is toxic to the cell [Figure 1].[16]{Figure 1}

By irradiation with light in the visible range of the spectrum, the dye (photosensitizer) is excited to its triplet state, the energy of which is transferred to molecular oxygen. The product formed is the highly reactive singlet oxygen capable of reacting with biological systems and destroying them. Only the first excited state with the energy of 94 kJ/mol (22 kcal/mol) above the ground state is important and the second excited state does not react.[17]

Mechanism of action

The three components of PDT are oxygen, photosensitizer, and light.

When a photosensitizer is administered to the patient and irradiated with a suitable wavelength, it goes to an excited state from its ground state. This excited state can then decay back to its ground state or form the higher energy triplet state.[18] The triplet state photosensitizer can react with biomolecules in two different pathways - type I and II.[19]

Type I: It involves electron/hydrogen transfer directly from the photosensitizer, producing ions, or electron/hydrogen removal from a substrate molecule to form free radicals. These radicals react rapidly with oxygen, resulting in the production of highly reactive oxygen species (superoxide, hydroxyl radicals, and hydrogen peroxide).

Type II: In type II reaction, the triplet state photosensitizer reacts with oxygen to produce an electronically excited and highly reactive state of oxygen, known as singlet oxygen (1 O2) which can interact with a large number of biological substrates inducing oxidative damage on the cell membrane and cell wall. Microorganisms that are killed by singlet oxygen include viruses, bacteria, and fungi. Singlet oxygen has a short lifetime in biological systems and a very short radius of action (0.02 mm). Hence, the reaction takes place within a limited space, leading to a localized response; thus making it ideal for application to localized sites without affecting distant cells or organs. Thus, the type II reaction is accepted as the major pathway in microbial cell damage.[20]

Light source

PDT requires a sources of light to activate the photosensitizer by exposure to low power visible light at a specific wavelength. Most photosensitizers are activated by red light between 630 and 700 nm, corresponding to a light penetration depth from 0.5 to 1.5 cm.[21] This limits the depth of necrosis. The total light dose, dose rates, and the depth of destruction vary with each tissue treated and photosensitizer used.[22] Currently, the light source applied in PDT are those of helium-neon lasers (633 nm), gallium-aluminum-arsenide diode lasers (630–690, 830, or 906 nm), and argon laser (488–514 nm), the wavelength of which range from visible light to the blue of argon lasers, or from the red of helium-neon laser to the infrared area of diode lasers.[23] Recently, nonlaser light source such as light-emitting diodes (LEDs), has been used as new light activators in PDT. LED devices are more compact, portable, and cost-effective compared to traditional lasers.[24]

Photosensitizers

An optimal photosensitizer must possess photo-physical, chemical, and biological characteristics. Most of the sensitizers used for medical purposes belong to the following basic structure:

Tricyclic dyes with different meso-atoms. E.g.: Acridine orange, proflavine, riboflavin, methylene blue, fluorescein, and erythrosine Tetrapyrroles. E.g.: Porphyrins and derivatives, chlorophyll, phylloerythrin, and phthalocyanines Furocoumarins. E.g.: Psoralen and its methoxyderivatives, xanthotoxin, and bergaptene.[25]

Photofrin and hematophyrin derivatives are referred to as first generation sensitizers. Second generation photosensitizers include 5-aminolevulinic acid (ALA), benzoporphyrin derivative, texaphyrin, and temoporfin (mTHPC). These photosensitizers have greater capability to generate singlet oxygen. Topical ALA has been used to treat precancer conditions, and basal and squamous cell carcinoma of skin.[26]

In antimicrobial PDT, photosensitizers used are toluidine blue O and methylene blue. Both have similar chemical and physicochemical characteristics. Toluidine blue O is a solution that is blue-violet in color. It stains granules within mast cells and proteoglycans/glycosaminoglycans within connective tissues. Methylene blue is a redox indicator that is blue in an oxidizing environment and becomes colorless upon reduction. Methylene blue combined with light has been reported to be beneficial in killing the influenza virus, Helicobacter pylori, and Candida albicans.[27] Methylene blue and toluidine blue O are very effective photosensitizing agents for the inactivation of both Gram-positive and Gram-negative periodontopathic bacteria. Tetracyclines used as antibiotics in periodontal diseases are also effective photosensitizers producing singlet oxygen.[28]

Application of photodynamic therapy

PDT can be considered as an adjunctive to conventional mechanical therapy. The technical simplicity and effective bacterial eradication are the two reasons why PDT is extensively studied in periodontics. Antimicrobial PDT not only kills the bacteria but may also lead to the detoxification of endotoxins such as lipopolysaccharide. These lipopolysaccharides treated by PDT do not stimulate the production of proinflammatory cytokines by mononuclear cells. Thus, PDT inactivates endotoxins by decreasing their biological activity.[29]

Scaling and root planning is to be carried out before PDT. While doing the PDT, the photosensitizer is first infused in the periodontal pocket and allowed to pigment for 2 min. Then the fiber is inserted 1 mm short of the pocket and lased by moving in a sinusoidal manner from side to side toward the coronal third.

Advantages of photodynamic therapy

Minimally invasive technique with least collateral damage to normal cells enhances results and superior healing Exceedingly efficient broad spectrum of action, since one photosensitizer can act on bacteria, virus, fungi, yeasts, and parasitic protozoa Efficacy independent of the antibiotic resistance pattern of the given microbial strain The therapy also causes no adverse effects such as ulcers, sloughing or charring of oral tissues Lesser chance of recurrence of malignancy Economical to use.[30]

Limitations of photodynamic therapy

Systemic administration of photosensitizer causes a period of residual skin photosensitivity due to the accumulation of photosensitizers under the skin. Therefore, photosensitizers can be activated by daylight causing first or second-degree burns. Hence, direct sunlight must be avoided for several hours until the drug is completely eliminated from the body.[30] Most of the dyes adhere strongly to the soft tissue surface of the pocket, even for a shorter period of time, may affect periodontal tissue attachment during wound healing.[2]

Future directions

Although the therapeutic potential of light-based treatments has been recognized for some time, the expansion of PDT has occurred only recently, due to its promising results and clinical simplicity. While PDT is currently applied mostly in oncological therapy, in the future, it will most likely be applied to other areas. Clinical PDT is continuing to grow because of the relatively recent availability of portable and dependable light sources.

The concept of photodynamic laser therapy itself is very attractive because it selects the target tissue by “marking” it with the photosensitizer and the therapy (laser energy) is active (focused) only on “marked” cells or tissues. Development of new photosensitizers, more efficient light delivery systems, and further animal studies are required to establish the optimum treatment parameters before investigators can proceed to clinical trials and eventual clinical use. The future of PDT will depend on the interactions between clinical applications and technological innovations.

Allison et al.[31] have described PDT as the therapy that “is truly the marriage of a drug and a light,” and as a result, only interdisciplinary research approaches can overcome all the difficulties and challenges of PDT.

 Conclusion



Antimicrobial PDT seems to be a unique and interesting therapeutic approach toward the periodontal therapy. There is a great need to develop an evidence-based approach to the use of PDT for the treatment of periodontitis and periimplantitis. However, the low wavelength lasers exhibiting deep tissue penetration basically do not interact with the periodontal tissues within the pocket. Therefore, PDT as a low-level therapy with short irradiation time does not produce any thermal change within the gingival tissue and root surface or destruction of the intact attachment apparatus at the base of pockets. PDT may be an effective way to treat the bacteria linked to periodontal diseases and could provide a better option than antibiotics or other mechanical methods for treating periodontal diseases and may prove to be a promising alternative to conventional periodontal therapy in near future.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Rajesh S, Koshi E, Philip K, Mohan A. Antimicrobial photodynamic therapy: An overview. J Indian Soc Periodontol 2011;15:323-7.
2Takasaki AA, Aoki A, Mizutani K, Schwarz F, Sculean A, Wang CY, et al. Application of antimicrobial photodynamic therapy in periodontal and peri-implant diseases. Periodontol 2000 2009;51:109-40.
3Polson AM, Frederick GT, Ladenheim S, Hanes PJ. The production of a root surface smear layer by instrumentation and its removal by citric acid. J Periodontol 1984;55:443-6.
4van Winkelhoff AJ, Rams TE, Slots J. Systemic antibiotic therapy in periodontics. Periodontol 2000 1996;10:45-78.
5López NJ, Gamonal JA, Martinez B. Repeated metronidazole and amoxicillin treatment of periodontitis. A follow-up study. J Periodontol 2000;71:79-89.
6Kornman KS, Page RC, Tonetti MS. The host response to the microbial challenge in periodontitis: Assembling the players. Periodontol 2000 1997;14:33-53.
7Wainwright M. Photodynamic antimicrobial chemotherapy (PACT). J Antimicrob Chemother 1998;42:13-28.
8Ochsner M. Photophysical and photobiological processes in the photodynamic therapy of tumours. J Photochem Photobiol B 1997;39:1-18.
9Sharwani A, Jerjes W, Salih V, MacRobert AJ, El-Maaytah M, Khalil HS, et al. Fluorescence spectroscopy combined with 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in detecting oral premalignancy. J Photochem Photobiol B 2006;83:27-33.
10Llano J, Raber J, Eriksson LA. Theoretical study of phototoxic reactions of psoralens. J Photochem Photobiol A Chem 2003;154:235-43.
11Daniell MD, Hill JS. A history of photodynamic therapy. Aust N Z J Surg 1991;61:340-8.
12Raab O. The effect of fluorescent agents on infusoria (in German). Z Biol 1900;39:524-6.
13Von Tappeiner H. Zur kenntis der lichtwirkenden (fluoreszierenden) stoffe. Dtsch Med Wochenschr 1904;16:1579-80.
14Dougherty TJ, Henderson BW, Schwartz S, Winkelman JW, Lipson RL. Historical perspective. In: Henderson BW, Dougherty TJ, editors. Photodynamic Therapy. New York: Marcel Dekker Inc.; 1992. p. 1-15.
15Wilson M. Photolysis of oral bacteria and its potential use in the treatment of caries and periodontal disease. J Appl Bacteriol 1993;75:299-306.
16Moan J, Peng Q. An outline of the history of PDT, in thierry patrice: Photodynamic therapy, comprehensive series in photochemistry and photobiology 2. Burlington House, Piccadilly, London: The Royal Society of Chemistry; 2003. p. 1-18.
17Konopka K, Goslinski T. Photodynamic therapy in dentistry. J Dent Res 2007;86:694-707.
18Ochsner M. Photodynamic therapy in squamous cell carcinoma. J Photochem Photobiol B 2001;52:42-8.
19Foote CS. Definition of type I and type II photosensitized oxidation. Photochem Photobiol 1991;54:659.
20Sharman WM, Allen CM, van Lier JE. Photodynamic therapeutics: Basic principles and clinical applications. Drug Discov Today 1999;4:507-17.
21Salva KA. Photodynamic therapy: Unapproved uses, dosages, or indications. Clin Dermatol 2002;20:571-81.
22Grant WE, Speight PM, Hopper C, Bown SG. Photodynamic therapy: An effective, but non-selective treatment for superficial cancers of the oral cavity. Int J Cancer 1997;71:937-42.
23Biel MA. Photodynamic therapy of head and neck cancers. Methods Mol Biol 2010;635:281-93.
24Juzeniene A, Juzenas P, Ma LW, Iani V, Moan J. Effectiveness of different light sources for 5-aminolevulinic acid photodynamic therapy. Lasers Med Sci 2004;19:139-49.
25Malik R, Manocha A, Suresh DK. Photodynamic therapy – A strategic review. Indian J Dent Res 2010;21:285-91.
26Allison RR, Cuenca RE, Downie GH, Camnitz P, Brodish B, Sibata CH. Clinical photodynamic therapy of head and neck cancers – A review of applications and outcomes. Photodiagnosis Photodyn Ther 2005;2:205-22.
27Lambrecht B, Mohr H, Knüver-Hopf J, Schmitt H. Photoinactivation of viruses in human fresh plasma by phenothiazine dyes in combination with visible light. Vox Sang 1991;60:207-13.
28Chan Y, Lai CH. Bactericidal effects of different laser wavelengths on periodontopathic germs in photodynamic therapy. Lasers Med Sci 2003;18:51-5.
29Kömerik N, Wilson M, Poole S. The effect of photodynamic action on two virulence factors of gram-negative bacteria. Photochem Photobiol 2000;72:676-80.
30Khandge NV, Pradhan S, Doshi Y, Kulkarni A, Dhruva I. Photodynamic therapy (Part I: Applications in dentistry). Int J Laser Dent 2013;3:7-13.
31Allison RR, Bagnato VS, Cuenca R, Downie GH, Sibata CH. The future of photodynamic therapy in oncology. Future Oncol 2006;2:53-71.