photodynamic therapy in periodontology.pptx

photodynamic therapy in periodontology

1. Photodynamic therapy Guided By- Dr. Srinivasa T. S MDS Guide, Professor &HOD Department of periodontology Presented By – Dr. Mangesh Andhare PG Student Department of periodontology

2. Contents Introduction History Mechanism Overview of clinical procedures PDT in periodontitis PDT in Peri- implantitis Photodynamic drug delivery Advantages Disadvantages Conclusion References

3. Introduction Recent years have seen an increased focus on using laser systems as an adjunct in periodontal therapy. In periodontics, the most commonly used lasers are high-power lasers. CO2, Nd:YAG, and Er:YAG lasers have been used for calculus removal, osseous surgery, and soft tissue management, such as Gingivectomy , gingival curettage , and melanin pigmentation removal .

4. Several studies have shown that processes such as inflammation, soft tissue and bone healing , and side effects such as postoperative pain and post treatment tooth hypersensitivity can be positively influenced by laser photo therapy ( LPT ). Because the antimicrobial activity of photo sensitizers is mediated by singlet oxygen , photodynamic antimicrobial chemotherapy (PACT) has a direct effect on extracellular molecules, and the polysaccharides of an extracellular polymeric matrix also are susceptible to photo damage.

5. Antioxidant enzymes, such as superoxide dismutase and catalase , protect against some oxygen radicals, but not against singlet oxygen . This dual activity, not displayed by antibiotics, represents a significant advantage of PACT. Photodynamic therapy Von Tappeiner coined the term Photodynamic to describe oxygen-consuming chemical reactions. in vivo Photodynamic therapy (PDT), also known as photo radiation therapy, phototherapy, or photo chemo –therapy.

6. definition it can be defined as eradication of target cells by reactive oxygen species produced by means of photosensitizing compound & light of appropriate wavelength (Raab et al 1900).

7. Photodynamic therapy (PDT) is the light induced non thermal inactivation of cells , microorganisms , or molecules. This utilizes light to activate a photosensitizing agent in the presence of oxygen. The exposure of the photo sensitizer to light results in the formation of toxic oxygen species , causing localized photo damage and cell death . Clinically, this reaction is cytotoxic and vasculotoxic. Depending on the type of agent, photo sensitizers may be injected intravenously , ingested orally , or applied topically.

8. HISTORY

9. Oscar Raab a German medical student observed death of Paramecium caudatum after light exposure in presence of acridine orange -1900 von Tappeiner & Jesionek (dermatologist) in 1904 used topical eosin and visible light to treat skin tumours, condyloma lata and lupus vulgaris 1942 – Auler/Banzer – tumour localizing properties of porphyrins 1960 - Lipson - localization of haematoporphyrin derivative ( HpD ) in neoplastic tissue.

10. Dougherty et al (Cancer Res 1978) pioneered the successful use of PDT to treat cutaneous cancer and other malignancies 1990 - Kennedy - Topical ALA-PDT in skin tumours Canada, France, Germany, Japan, The Netherlands and U.S. have approved PDT for treating selective malignancies- intraoperatively and intracavitary use & Investigational treatment in psoriasis vulgaris, warts, diseases of epidermal appendages, atherosclerosis and rheumatoid arthritis, bacterial infection.

11. Components of PDT

12. General Requirements Of A Photosensitiser For Fighting Bacteria Photo-active with suitable laser Non-toxic Simple, drop-free, safe application Moistening With controlled viscosity Can also be used on open wounds No side effects Stable over time

13. The Requirements Of An Optimal Photosensitizer Include Photo-physical, Chemical, And Biological Characteristics: Highly selective tumor accumulation Low toxicity and fast elimination from the skin and epithelium Optimum ratio of the fluorescence quantum yield to the inter conversion quantum yield ( the first parameter determines the photosensitizer diagnostic capabilities, and plays a key role in monitoring the photosensitizer accumulation in tissues and its elimination from them; the second parameter determines the photosensitizer ability to generate singlet oxygen. )

14. High quantum yield of singlet oxygen production in vivo Cost effectiveness and commercial availability High solubility in water, injection solutions, and blood substitutes Storage and application light stability.

15. DYES (PHOTOSENSITIZER) I st generation : Photofrin (dihematoporphyrin ether) II nd generation : 5- aminolevulinic acid (ALA), benzoporphyrin derivative (BPD), lutetium texaphyrin, temoporfin , tinethyletiopurpurin (SnET2), and talaporfin sodium (LS11). Foscan® III rd generation : Third-generation photosensitizers include currently available drugs that are modified by targeting with monoclonal antibodies or with nonantibody - based protein carriers and protein/receptor systems, and conjugation with a radioactive tag.

16. (1) Dyes: tricyclic dyes with different meso-atoms – methylene blue, toludine blue O and acridine orange; and phthalocyanines – aluminum disulphonated phthalocyanine and cationic Zn(II)-phthalocyanine; (2) Chlorines: chlorine e6, stannous (IV) chlorine e6 (3) Xanthenes: erythrosine; and (4) Monoterpene: azulene.

17. Currently, only four photo sensitizers are commercially available: Photofrin® , ALA , Visudyne TM (BPD; Verteporfin), and Foscan® . The first three have been approved by the FDA, while all four are in use in Europe.

18. SOURCE OF LIGHT We have three light systems for the therapy: • Diode laser systems: They are easy to handle, portable, and cost effective. • Non coherent light sources: Preferred for treatment of larger areas and include tungsten filament , quartz halogen, xenon arc, metal halide , and phosphor coated sodium lamps. • Non laser light sources include light emitting diodes (LEDs)-They are economical, light weight, and highly flexible.

19. Sources of light include a range of lasers, helium lasers (633 nm), gallium – aluminum arsenide diode lasers (630-690, 830 or 906 nm) and argon laser (488-514nm), The wavelength of which range from visible light to the blue of argon lasers, or from red of helium-neon laser to the infra red area of diode lasers. Non-laser light sources like light emitting diode (LED)and light cure units. Photosensitizers are activated by red light between 630 and 700 nm corresponding to a light penetration depth from 0.5 cm (at 630 nm) to 1.5 cm at (700 nm) which is sufficient for periodontal treatment.

20. LASERS At present, diode laser systems that are easy to handle, portable, and cost-effective are used predominantly ( Kübler , 2005). Recently, non-laser light sources, such as light-emitting diodes (LED), have also been applied in PDT. These light sources are much less expensive and are small, lightweight, and highly flexible.

21. Although modern fiber-optic systems and different types of endoscopes can target light more accurately to almost any part of the body, custom-sized and custom-shaped fibers are needed to achieve more homogenous illumination ( Brown et al., 2004; Allison et al., 2006) Two other issues related to the use of light sources in PDT are: ( i ) the accurate calibration of any light source used, and (ii) monitoring of both light and drug delivery (drug and light dosimetry ). Devices that could simultaneously monitor both light delivery and sensitizer fluorescence would greatly advance PDT as a more routine clinical treatment.

22. Laser Systems Must Satisfy The Following Demands For The Correct Light: Appropriate wavelength and surface energy Glare-free light cable Can be used in sterile environment Simple, precise interlinking mechanism of the components If possible, high light power - at the end Light distribution suitable for therapy Adequate exposure of three dimensional and two dimensional structures

23. mechanism PDT induced effects mediated by photo-oxidative reactions, type I & II of which II is more important.

24. In type I, peroxide, superoxide and hydroxyl ions Photosensitizer absorbs light(energy) - excited(triplet) state. Energy transferred to molecular O2( type II photoxidative reaction) -singlet oxygen(reactive O2 spp.) Biologic effects: Primary cytotoxic Secondary vasculotoxic (systemic PDT) No DNA damage primarily, so no risk of mutations or carcinogenesis

25. mechanism

26. Kill tumor cells by: Induction of apoptosis and necrosis Damages the vasculature and the surrounding healthy vessels - Induction of hypoxia and starvation Initiate an immune response against remaining tumor cells

27. The chemical-/physical events in 3 steps Step 1: Staining of the microorganisms Step 2: Exposure and activation of the photosensitiser Step 3: Oxygen radical formation and destruction of the microorganisms

28. Step 1: Staining the microorganisms Diffusion -determining step with migration and attachment of the dye molecules on the wall of the microorganisms. Process parameters = Viscosity, pH-value, temperature, charge, time, structure of the plaque etc.

29. Step 2: Exposure and activation of the photosensitiser Energy-controlled step Determined by physical-optical properties with excitation of the sensitizer molecules from singlet state to triplet state. Process parameters: optical, electronic/ chemical states, pH-value, time etc.

30. Step 3: Oxygen radical formation and destruction of the microorganisms Formation of singlet-oxygen radicals and oxidative destruction of membrane lipids and enzymes Process parameters: electronic/chemical states, pH-value, time etc.

31. Integration Of PDT Into The Conventional Periodontitis Treatment

32. Overview of The Clinical Procedure Starting point: Painfully swollen, red gingiva Professional cleaning is fundamentally required Pathogenic test organisms still present after cleaning!

33. Overview Of The Clinical Procedure Application of the photosensitizer leads to staining of the microorganisms; N.B.: apply from the pocket fundus to the crown! Staining the microorganisms Reaction time 1-3 min, then rinse

34. Overview Of The Clinical Procedure Circular exposure with the LASER => min. 1 min per tooth/cm 2 Attack by oxygen radicals leads to the destruction of the bacteria Pre- exposure with the LASER => Rinse to reduce the coating density!

35. Overview of the clinical procedure Condition after approx. 12h Condition after 3 days

36. The photosensitiser only seeps a maximum of 2 cell layers (=12µm) into the tissue Eukaryotic cells (multi-cellular) have a defence system against radicals: the enzymes Superoxide dismutase Catalysis Peroxidases There for There is no danger for healthy cells

37. Frequency of Applications Normally one application is sufficient to achieve a very good result. In case of a refractory inflammation the application should be repeated after one week.

38. Biological Target Molecules Achieved Through The Radical Reactions carbohydrate bonds are rarely damaged by oxygen radicals, in the case of lipids, there is great damage. Since lipids are a major component of membranes (e.g. cell membranes), very sensitive disturbances to the membrane properties can be caused. Gram-positive bacteria membrane Gram-negative bacteria membrane

39. Particularly susceptible to damage by oxygen radicals are unsaturated fatty acids in the membranes.

40. “The antimicrobial photodynamic therapy destroys the proteolytic domain of at least one important protease of Porphyromonas gingivalis. In addition, the photodynamic treatment also destroys the Hemagglutinin - domain of at least one important protease. Thus, not only is the bacterium reduced, but also its important enzymes which promote the implantation of the bacterium and destroy the connective tissue of the host and which inhibit the body‘s own defences are destroyed. Identification of photolabile outer membrane Proteins of Porphyromonas Gingivalis”, Bhatti M, Nair SP, MacRobert AJ, Henders , In: Curr Microbiol., Vol. 43/2 (2001) pp. 96-99

41. success parameters! Reaction time of the photosensitiser min. 60sec.! Longer is no problem; depending on the clinical situation (deep pocket > 6mm) the reaction time should even be extended to 2-3min. Pre- exposure: Rinse well!!! A coating density of a hair‘s breadth leads to 95% absorption of the light! Exposure time per tooth / per cm 2 min. 60sec., that corresponds to approx. 3 J/cm 2 . An exposure time of > 120sec. Should not be exceeded however. The system components are fitted together – a change to the parameters endangers the success of the therapy!

42. PDT In Chronic Periodontitis P.gingivalis is the predominant organism found in chronic periodontitis. This organism contains a group of proteases known as gingipains on bacterial cell surface. When the polycationic macromolecule PLC E 6 conjugate comes in contact with the outer membrane of P.gingivalis, poly-L-lysine binds to the anionic sites of LPS present on the cell wall by electrostatic attraction. Then the photosensitizer chlorine C E 6 enters the cell & causes cell lysis on exposure to red light.

43. In patients with chronic periodontitis, clinical outcomes of conventional subgingival debridement can be improved by adjunctive aPDT . Andreas Braun, Claudia Dehn 2008 Streptococcus sanguis is destroyed by the photosensitizer toludine blue in presence of diode laser

44. PDT & Alveolar Bone Loss Significant reduction in alveolar bone loss was observed when PDT was used in combination with photosensitizer & laser rather than alone 1,2 1 Wilson et al; 1989. 2 de Almeida JM, Theodoro LH, Bosco AF, Nagata MJ, Oshiiwa M, Garcia VG; 2008.

45. PDT In Aggressive Periodontitis A.a is the predominant organism found in aggressive periodontitis. The PDT effect of cationic conjugate on A.a was found to be due to the electrostatic attraction between the conjugate & negatively charged membrane of the bacterium. A reduction of 60 % in survival of A.a was achieved after treatment with visible light of 12 j/cm 2 with C E 6 However, PDT and SRP showed similar clinical results in the non-surgical treatment of aggressive periodontitis. Rafael R. de Oliveira; 2007

46. PDT In Peri-implantitis Photodynamic therapy is a non-invasive method that could be used to reduce microorganisms in peri-implantitis . Ricardo R.A. Hayek; 2005 The lethal photosensitization associated with GBR allowed for better re- osseointegration at the area adjacent to the peri -implant defect regardless of the implant surface. Shibli JA, Martins MC; 2006

47. With the relatively poor success of systemic antibiotic therapy in the treatment of peri-implantitis and the continued increase in antibiotic resistant bacteria on a global level, photodynamic therapy as a local treatment for peri-implantitis has potential as a viable treatment alternative. Numerous studies have proven the success of PDT in the reduction of plaque associated bacteria in natural teeth and implant fixtures .

48. Photodynamic Drug Delivery Into Oral Microbial Biofilms Nikolaos et al 1999 published the first report to show that the permeability of a microbial biofilm increases on exposure to single photomechanical waves. The photosensitizer compound methylene blue was used for 2 reasons : it was an organic dye with fluorescent & photosensitizing properties which inactivates viruses & bacteria on exposure to light. The photomechanical waves enhanced fluid forces at bio film water interface that deform microcolonies of bacteria & the matrix so that fluid movements occurs.

49. This process requires the presence of drug methylene blue for 5 min & exposure of photomechanical waves for 110 ns. This approach of using photomechanical waves could prove useful in delivering drugs into oral biofilms. Further studies are required to explore synergistic effect of photomechanical waves & red light on biofilms consisting of single/multiple species.

50. Advantages Relatively selective treatment Non-invasive Multiple lesions may be treated simultaneously Safe Supervised outpatient procedure Repeated treatments possible Minimal or no scarring, good/excellent cosmetics The rapid application of drug into the periodontal pocket resulted in rapid killing of bacteria & there is no development of resistance There was no ulcer formation on the epithelium & no inflammation, in the connective tissue even with highest photosensitizer concentration

51. Disadvantages Allergic reactions like urticaria to photosensitizer Can aggravate SLE Light (laser) overdose causes blistering, ulceration or excessive necrosis

52. CONCLUSION The application of photomechanical drug delivery proved to be a valuable alternative or supplement to various surgical procedures & other modalities of therapy than combined with scaling & root planing. The results of various studies suggested that further investigation in this novel approach to antimicrobial therapy is worth undertaking.

53. Even though PDT is still in experimental stages of development and testing, the method may be an adjunct to conventional antibacterial measures in periodontology. Further studies are required to determine whether repeated applications of PDT leads to a greater reduction in bone loss & to establish optimum treatment parameters before proceeding to luminal trials.

54. references Christodoulides N et al. Photodynamic Therapy as an Adjunct to Non-Surgical Periodontal Treatment: A Randomized, Controlled Clinical TrialJ Periodontol 2008;79:1638-1644. Raghavendra M, Koregol A , Bhola S. Photodynamic therapy: a targeted therapy in periodontics. Australian Dental Journal 2009;54:02–109. Shivakumar V, Shanmugam M, Sudhir G, Priyadarshoni SP. Scope of photodynamic therapy in periodontics and other fields of dentistry. J Interdiscip Dentistry 2012;2:78-83 . Saxena S, Bhatia G, Garg B, Rajwar Yc . Role Of Photodynamic Therapy In Periodontitis. Asian Pac. J. Health Sci., 2014;1:200-206. Bhatti M, Nair SP, MacRobert AJ, Henders , Identification of photolabile outer membrane Proteins of Porphyromonas Gingivalis In: Curr Microbiol . 2001; 43 : 96-99.

55. Thank you!