Photodynamic therapy seminar.pptx in perio

Photodynamic therapy seminar.pptx in perio

1. PHOTODYNAMIC THERAPY Dr. Nihal Abbas (PG-2) Department of Periodontology Guide: Dr. M M Dayakar

2. contents Introduction History Components of PDT Mechanism of action Uses Advantages Disadvantages Complications or Side effects Use in periodontal diseases Future of PDT Conclusion References 2

3. introduction Photodynamic therapy (PDT), is a form of phototherapy involving light and a photosensitizing chemical substance, used in conjunction with molecular oxygen to elicit cell death ( phototoxicity ). The  P hotosensitizing agent , concentrates selectively in certain cells , which is followed by exposure of the involved tissue to a light source (such as laser or ultraviolet light ). 3 AlAhmari F, Shaikh L, AlDhubaiban D. Photodynamic therapy in the treatment of periodontal diseases: A review. Journal of International Oral Health. 2020 Mar 1;12(2):102

4. Historical Background 6000 years ago to the ancient Egyptians used light‑sensitive substances (psoralens) by crushing leaves of plants related to parsley with sunlight to treat sunburns . Use of a plant extract for the restoration of skin pigmentation- 1400 BC Phototoxic effects of psoralens were described in 1250 AD. PDT was first reported by the Danish physician, Niels Finsen. 4 Photodynamic Therapy (Part 1: Applications in Dentistry) Nikhil Vishwas Khandge, Suchetan Pradhan, Yogesh Doshi, Atul Kulkarni, Ishan Dhruva

5. Historical Background Oscar Raab (1900): The concept of cell death induced by the interaction of light and chemicals. Von tappiener ( 1905): coined the term “Photodynamic action” and showed that oxygen was essential. Samuel schwartz (1960): Discovery of hematoporphyrins. In the recent past many combinations of lasers and photosensitizers were tried with different parameters varying success. 5

6. Components OF PDT PDT has three essential components:- 1. PHOTOSENSITIZER 2. LIGHT SOURCE 3. MOLECULAR OXYGEN 6 Kumar V, Sinha J, Verma N, Nayan K, Saimbi CS, Tripathi AK. Scope of photodynamic therapy in periodontics. Indian Journal of Dental Research. 2015 Jul 1;26(4):439 .

7. PHOTOSENSITIZER A photosensitizer is a molecule that produces a chemical change in another molecule by a photochemical process.  They are divided into  Chlorin, Phthalocyanine, and Porphyrin A wide array of photosensitizers for PDT exist . FIRST GENERATION • Porfimer sodium(M/C) • Hematoporphyrins 7 SECOND GENERATION • Aminolevulinic acid(ALA) • meso-Tetrahydroxyphenylchlorin(mthpc) • Benzoporphyrin derivative(BPD) Kumar V, Sinha J, Verma N, Nayan K, Saimbi CS, Tripathi AK. Scope of photodynamic therapy in periodontics. Indian Journal of Dental Research. 2015 Jul 1;26(4):439 .

8. NEWER PHOTOSENSITIZER • Tin ethyl etiopurpurin (SnET2) • Mono-L-aspartyl chlorin e6(Npe6) • Lutetium texaphyrin (Lu- Tex ) PHOTOSENSITIZER COMMERCIALLY AVAILABLE FOR CLINICAL USE :- • Allumera • Photofrin • Foscan • Levulan • Metvix 8 Kumar V, Sinha J, Verma N, Nayan K, Saimbi CS, Tripathi AK. Scope of photodynamic therapy in periodontics. Indian Journal of Dental Research. 2015 Jul 1;26(4):439 .

9. Ideal requirements of photosentitizer agents Should be able to preferentially accumulate in diseased tissue and induce a desired biological effect via the generation of cytotoxic species Selectivity to diseased cells, tissues. Preferential accumulation in diseased/target tissue over healthy tissue Photo stability Biological stability Simple and stable formulation Photochemical efficiency Should not produce cytotoxicity in the absence of light Strong absorption Good tissue penetration Rapid clearance from the body post-procedure 9

10. LIGHT PDT requires a source of light to activate the photosensitizer at a specific wavelength.  Each PS has specific wavelength and intensity of light activation. 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. The total light dose, dose rates, and the depth of destruction vary with each tissue treated and photosensitizer used. Helium – neon lasers, Gallium – aluminum – arsenide diode lasers, Argon laser. N on laser light source, such as light – emitting diodes (LED) 10 Borgia F, Giuffrida R, Caradonna E, Vaccaro M, Guarneri F, Cannavò SP. Early and late onset side effects of photodynamic therapy. Biomedicines. 2018 Mar;6(1):12.

11. MOLECULAR OXYGEN When a photosensitizer is in its excited state it can interact with molecular triplet oxygen ( 3 O 2 ), produce radicals and reactive oxygen species (ROS). These species include: Singlet oxygen ( 1 O 2 ) Hydroxyl radicals (OH )  Superoxide (O 2 − ) ions. 11 Borgia F, Giuffrida R, Caradonna E, Vaccaro M, Guarneri F, Cannavò SP. Early and late onset side effects of photodynamic therapy. Biomedicines. 2018 Mar;6(1):12.

12. MECHANISM OF ACTION The PDT is defined as an oxygen-dependent photochemical reaction  Light – mediated activated photosensitizer compound reacts with oxygen to produce an electronically excited and highly cytotoxic reactive oxygen species, known as singlet oxygen. Microorganisms that are killed by singlet oxygen include viruses, bacteria, and fungi. The reaction takes place within a limited space, leading to a localized response. 12 Kumar V, Sinha J, Verma N, Nayan K, Saimbi CS, Tripathi AK. Scope of photodynamic therapy in periodontics. Indian Journal of Dental Research. 2015 Jul 1;26(4):439 .

13. TYPE I REACTION :- • Direct reaction with substrate (cell membrane or molecule) • Transfer of H atom to form radicals • Radical react with O2 to form oxygenated products TYPE II REACTION:- Transfer of oxygen to form singlet oxygen Both Type-I and II pathways play a pivotal role in disrupting cellular mechanisms and cellular structure. Type-II photo-oxygenation process predominates in the induction of cell damage. Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, Moan J, Peng Q. Photodynamic therapy. JNCI: Journal of the national cancer institute. 1998 Jun 17;90(12):889-905 . 13

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15. Singlet oxygen is a very aggressive chemical species and will very rapidly react with any nearby biomolecules. Ultimately, these destructive reactions will kill cells through apoptosis or necrosis. 2 types of cytotoxicity is presented by the Oxygen species: 15 DIRECT CYTOTOXICITY IN DIRECT CYTOTOXICITY Direct tumor cell killing is due to macromolecule damage Apoptosis Necrosis Changes in tumor/tissue microenvironment Antivascular effect Antitumor immune responses

16. DIRECT CYTOTOXICITY The lifetime of singlet oxygen is 0.03 to 0.18 mcs . Thus the macromolecular damage inside cell occurs fast & very close to location of photosensitizer activation/singlet oxygen production. APOPTOTIC cell death predominate at lower light/photosensitizer doses NECROTIC cell death tend to predominate at higher light/photosensitizer doses Some recent studies have indicated that autophagy is also involved in PDT-induced cell death. 16 Borgia F, Giuffrida R, Caradonna E, Vaccaro M, Guarneri F, Cannavò SP. Early and late onset side effects of photodynamic therapy. Biomedicines. 2018 Mar;6(1):12.

17. INDIRECT CYTOTOXICITY Anti- T umor Immune Response:- • Release of pro-inflammatory cytokines • Fixation of complement • Release of tumor associated antigens Anti-Vascular Effect:- • Vessel Leakage • Vasoconstriction • Thrombosis 17 Borgia F, Giuffrida R, Caradonna E, Vaccaro M, Guarneri F, Cannavò SP. Early and late onset side effects of photodynamic therapy. Biomedicines. 2018 Mar;6(1):12.

18. Applications of PDT Photodynamic Therapy  is a modern treatment for various health and cosmetic conditions. ONCOLOGY Esophageal cancer, Mouth Cancer And Lung Cancer Basal Cell Carcinoma  Bowens disease Actinic Keratosis Barrett's esophagus Extra mammary Paget's disease In addition to directly killing cancer cells, PDT appears to shrink or destroy tumors. Blant SA, Woodtli A, Wagnières G, Fontolliet C, van den Bergh H, Monnier P. In vivo fluence rate effect in photodynamic therapy of early cancers with tetra (m‐ hydroxyphenyl ) chlorin . Photochemistry and photobiology. 1996 Dec;64(6):963-8. 18

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20. SKIN CONDITIONS Mainly in treatment of basal cell skin cancers.  Used to deal with the effects of scarring, to remove some types of blemishes,  treatment of severe acne and acne scarring. Used for Photorejuvenation of skin. 20

21. DENTISTRY Applications of PDT in dentistry are growing rapidly T reatment of oral leukoplakia, oral lichen planus, and head & neck cancer PDT is potential adjuvant to maximize the oral disinfection of microorganisms responsible for dental caries. PDT has good results against the main cariogenic bacteria ( Streptococcus mutans ) It is useful as a minimally invasive adjuvant therapy for the control of dental caries through cariogenic bacteria inactivation 21

22. Photodynamic antimicrobial chemotherapy (PACT) has been efficacious in the treatment of bacterial, fungal, parasitic, and viral infections.  Photosensitizers used in PACT include: Methylene Blue (MB) Toluidine Blue O (TBO) chlorine Polylysine Management of oral biofilms. Elimination of periodontal pockets. Treatment of Chronic and Aggressive Periodontitis. Nagata JY, Hioka N, Kimura E, Batistela VR, Terada RS, Graciano AX, Baesso ML, Hayacibara MF. Antibacterial photodynamic therapy for dental caries: evaluation of the photosensitizers used and light source properties. Photodiagnosis and photodynamic therapy. 2012 Jun 1;9(2):122-31 . de Oliveira AB, Ferrisse TM, Marques RS, de Annunzio SR, Brighenti FL, Fontana CR. Effect of photodynamic therapy on microorganisms responsible for dental caries: A systematic review and meta-analysis. International journal of molecular sciences. 2019 Jan;20(14):3585. 22

23. Advantages of Photodynamic Therapy over Conventional Therapies • Is non-invasive and convenient for the patient • Can be performed in outpatient or day-case (inpatient) settings • Can be targeted accurately and selectively in early or localized diseases • Although it cannot cure advanced disseminated disease, it can improve quality of life and lengthen survival. • Repeated doses can be given without the need for total-dose limitations • Has moderate side-effects • Can have excellent cosmetic results, and the healing process results in little or no scarring • Can offer organ-sparing treatment worldwide, with very little investment in infrastructure Raghavendra M, Koregol A, Bhola S. Photodynamic therapy: a targeted therapy in periodontics. Australian dental journal. 2009 Sep;54:S102-9. 23

24. limitations The light needed to activate most photosensitizers cannot pass through more than about one-third of an inch of tissue. For this reason, PDT is usually used to treat tumors on or just under the skin or on the lining of internal organs or cavities. PDT is also less effective in treating deeper extensive tumors, because the light cannot pass far into these tumors. The photosensitizers in some cases, might be harmful as the normal cells feed up on it. When used to treat skin conditions The skin might burn or blister or swell if exposed to direct sunlight . Raghavendra M, Koregol A, Bhola S. Photodynamic therapy: a targeted therapy in periodontics. Australian dental journal. 2009 Sep;54:S102-9. 24

25. Side effects of pdt EARLY ONSET SIDE EFFECTS The most common side effect of PDT is sensitivity to bright lights and sunlight.  Pain and Local Skin Reactions (LSRs), including erythema, edema, desquamation. Erythema and edema are the main phototoxic effects of PDT and develop in the treated area during and after light exposure. Rarely, urticaria, contact dermatitis, or erosive pustular dermatosis of the scalp (EPDS) occur. Borgia F, Giuffrida R, Caradonna E, Vaccaro M, Guarneri F, Cannavò SP. Early and late onset side effects of photodynamic therapy. Biomedicines. 2018 Mar;6(1):12. 25

26. PDT has a significant effect on the immune system, by either stimulating or repressing innate and adaptive immune response. O ccurrence of infections at the site of treatment is a rare complication, with only four cases of bacterial cellulitis reported in over 700 treatments. Other side effects of PDT are related to the area that is treated. They can include coughing, trouble swallowing, stomach  pain, painful breathing, or shortness of breath; these side effects are usually temporary. LATE ONSET SIDE EFFECTS Pigment c hanges and scarring Bullous Pemphigoid Carcinogenicity- Long term photosensitization can sometimes cause DNA damage and oncogene activation. 26

27. Photodynamic therapy in periodontal diseases 27

28. Periodontitis is a chronic, multifactorial and polymicrobial inflammatory disease. The presence of periodontopathogenic bacteria, include: Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) Porphyromonas gingivalis Treponema denticola (T. denticola) Tannerella forsythia Treatment for periodontitis is focused on the reduction or elimination of the supragingival and subgingival microbial biofilm. 28 Raghavendra M, Koregol A, Bhola S. Photodynamic therapy: a targeted therapy in periodontics. Australian dental journal. 2009 Sep;54:S102-9.

29. A reduction in the subgingival biofilm can be achieved by various Non Surgical Periodontal therapies. Photodynamic therapy (PDT) has been proposed as an adjunctive approach to nonsurgical periodontal treatment in patients with periodontitis. Photodynamic antimicrobial chemotherapy represents an alternate antibacterial, antifungal, and antiviral treatment against drug - resistant organisms. Antimicrobial PDT not only kills the bacteria but may also lead to the detoxification of endotoxins such as lipopolysaccharide. 29 Raghavendra M, Koregol A, Bhola S. Photodynamic therapy: a targeted therapy in periodontics. Australian dental journal. 2009 Sep;54:S102-9.

30. Mechanism of a photodynamic therapy aPDT requires the use of a light with wavelength ranging from 635 to 690 nm, photosensitizing agent, and oxygen inside the cells. Photosensitizing agents that are used in periodontal therapy such as M ethylene blue, Phenothiazinium chloride, Indocyanine green T oluidine blue Tetracycline used as antibiotics in periodontal diseases are also effective photosensitizers producing singlet oxygen. 30 Raghavendra M, Koregol A, Bhola S. Photodynamic therapy: a targeted therapy in periodontics. Australian dental journal. 2009 Sep;54:S102-9.

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33. There are many parameters influencing photo-damage: D ose , and type of light source L ight power density, Wavelength of light A vailability of oxygen and location of the photosensitizer I ncubation time Dual selectivity is known to be the significant characteristic of PDT. It is achieved by control of light delivery and increasing the selective accumulation of photosensitizers in the diseased tissues. Raghavendra M, Koregol A, Bhola S. Photodynamic therapy: a targeted therapy in periodontics. Australian dental journal. 2009 Sep;54:S102-9. 33

34. a photodynamic therapy for the treatment of chronic periodontitis Mechanical treatment alone cannot entirely eliminate the pathogens from periodontal tissues. The limitations of traditional periodontal therapy led to use of PDT as conjunctive therapy for chronic periodontitis. The advantage of PDT over other therapies is that it has dual selectivity, which limits the damage to the normal tissues. Found to reduce pain, promote faster healing, and aid in hemostasis. 34 Raghavendra M, Koregol A, Bhola S. Photodynamic therapy: a targeted therapy in periodontics. Australian dental journal. 2009 Sep;54:S102-9.

35. Photosensitizers such as phenothiazines , phthalocyanines , and porphyrins can target both gram negative and gram-positive bacteria. Toluidine blue O reacts even in the absence of light with lipopolysaccharides that exist in the gram-negative bacteria cell membrane. L ight having wavelength from 380 to 520 nm stimulates a threefold decrease in the growth of Prevotella melaninogenica , P. nigrescens , P. intermedia , and Porphyromonas gingivalis Kumar V, Sinha J, Verma N, Nayan K, Saimbi CS, Tripathi AK. Scope of photodynamic therapy in periodontics. Indian Journal of Dental Research. 2015 Jul 1;26(4):439 . 35

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38. a photodynamic therapy for the treatment of aggressive periodontitis To reduce the bacterial load, antimicrobial photodynamic therapy (aPDT) has been proposed as a treatment strategy for AgP. aPDT is effective in reducing numbers of A. actinomycetemcomitans Study by Arthur B. Novaes Jr states that combination of a photosensitizer with low-power laser irradiation was effective in killing/ almost completely eliminating A. actinomycetemcomitans, P. gingivalis, and F. nucleatum aPDT also showed significant improvement in the clinical periodontal parameters. Novaes AB, Schwartz- Filho HO, de Oliveira RR, Feres M, Sato S, Figueiredo LC. Antimicrobial photodynamic therapy in the non-surgical treatment of aggressive periodontitis: microbiological profile. Lasers in medical science. 2012 Mar 1;27(2):389-95 . 38

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40. a Pdt for pocket elimination STEPS: Periodontal sites were irrigated with 1 ml of the photosensitizer liquid using a blunt needle Three minutes later(incubation period), all pockets were thoroughly rinsed with sterile saline to remove any excess photosensitizer liquid Immediately after rinsing, diode laser red (wavelength of 660 nm) and infrared (wavelength of 808 nm) are simultaneously applied inside the periodontal pocket. The laser equipped with a probe tip that was placed at the pocket depth and moved circumferentially around the tooth for 1 min. 40 Novaes AB, Schwartz-Filho HO, de Oliveira RR, Feres M, Sato S, Figueiredo LC. Antimicrobial photodynamic therapy in the non-surgical treatment of aggressive periodontitis: microbiological profile. Lasers in medical science . 2012 Mar 1;27(2):389-95 .

41. Advantages of a photodynamic therapy in periodontics 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. 41

42. Development of resistance to the PDT is less As PDT is non-invasive local therapy, disturbances of the microflora at other sites would not occur and damage to the adjacent host tissues can be avoided. PDT offers thorough irrigation and elimination of pathogens in inaccessible areas of periodontal pocket within short span of time. The risk of bacteremia after periodontal debridement can be minimized. There is no need to prescribe antibiotics, therefore the possibilty of side effects is avoided. There is no need to anaesthetize the area and destruction of bacteria is achieved in a very short period (<60 seconds). AlAhmari F, Shaikh L, AlDhubaiban D. Photodynamic therapy in the treatment of periodontal diseases: A review. Journal of International Oral Health. 2020 Mar 1;12(2):102. 42

43. Risk and side effects of a photodynamic therapy Undesirable photo-allergic and phototoxic side effects with respect to the photodynamic action. Chance of thermogenesis Long-time irradiation of the laser at the same site may cause lesions on dental pulp, bone, or other deeper tissues. PDT is also associated with risks and side effects related to light energy, photosensitizer, and related photochemical reaction However systemic side effects are rare. AlAhmari F, Shaikh L, AlDhubaiban D. Photodynamic therapy in the treatment of periodontal diseases: A review. Journal of International Oral Health. 2020 Mar 1;12(2):102. 43

44. Future of photodynamic therapy 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. Clinical PDT is continuing to grow because of the relatively recent availability of portable and dependable light sources. A new concept has been proposed that PDT‐induced acute inflammation can mediate neutrophil infiltration to deliver therapeutics in deep tumor tissues. Combination of PDT and immunotherapies has shown the promising translation of PDT for cancer therapies A new area in PDT is to treat bacterial infections to overcome the antimicrobial resistance. 44

45. Recent progress in the development of photosensitizers, in particular, is photosensitizers with nanoparticle modifications. An activatable photosensitizer whose photo-activity could be turned on by a specific disease biomarker that is capable of distinguishing healthy cells from diseased cells, thereby reducing off‐target photo-damage. Allison et al. (2006) 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. Liu M, Li C. Recent Advances in Activatable Organic Photosensitizers for Specific Photodynamic Therapy. ChemPlusChem . 2020 May 1. 45

46. conclusion Photodynamic therapy is based on the concept: certain photosensitizers can be localized in neoplastic/diseased tissue, and these photosensitizers can be activated with the appropriate wavelength of light to generate active molecular species, such as free radicals and singlet oxygen that are toxic to cells and tissues. PDT has proven ability to kill microbial cells including bacteria, fungi and viruses. In PDT, the usage of the right wavelength of the light, the correct light-sensitive compounds which are at the same time highly effective to treat the targeted tissue is an important step that needs to be followed. 46

47. Antimicrobial PDT seems to be a unique and interesting therapeutic approach toward the periodontal therapy. 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 is 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. PDT offers advantages particularly in avoiding emergence of antibiotic resistance species, requiring less technical skills and reducing operating time. 47

48. Researchers continue to study ways to improve the effectiveness of PDT and expand it to other fields of medicine. Researches are focused on the development of Photosensitizers that are more powerful, more specifically target cancer cells, and are activated by light that can penetrate tissue and treat deep or large tumors. Development of new photosensitizers, more efficient light delivery systems and further clinical studies are required to establish the optimum treatment parameters for PDT. 48

49. references AlAhmari F, Shaikh L, AlDhubaiban D. Photodynamic therapy in the treatment of periodontal diseases: A review. Journal of International Oral Health. 2020 Mar 1;12(2):102 Borgia F, Giuffrida R, Caradonna E, Vaccaro M, Guarneri F, Cannavò SP. Early and late onset side effects of photodynamic therapy. Biomedicines. 2018 Mar;6(1):12. Kumar V, Sinha J, Verma N, Nayan K, Saimbi CS, Tripathi AK. Scope of photodynamic therapy in periodontics. Indian Journal of Dental Research. 2015 Jul 1;26(4):439 . Raghavendra M, Koregol A, Bhola S. Photodynamic therapy: a targeted therapy in periodontics. Australian dental journal. 2009 Sep;54:S102-9. Blant SA, Woodtli A, Wagnières G, Fontolliet C, van den Bergh H, Monnier P. In vivo fluence rate effect in photodynamic therapy of early cancers with tetra (m‐ hydroxyphenyl ) chlorin . Photochemistry and photobiology. 1996 Dec;64(6):963-8. 49

50. Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, Moan J, Peng Q. Photodynamic therapy. JNCI: Journal of the national cancer institute. 1998 Jun 17;90(12):889-905. Novaes AB, Schwartz- Filho HO, de Oliveira RR, Feres M, Sato S, Figueiredo LC. Antimicrobial photodynamic therapy in the non-surgical treatment of aggressive periodontitis: microbiological profile. Lasers in medical science. 2012 Mar 1;27(2):389-95 . Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nature reviews cancer. 2023 May;3(5):380-7. Nagata JY, Hioka N, Kimura E, Batistela VR, Terada RS, Graciano AX, Baesso ML, Hayacibara MF. Antibacterial photodynamic therapy for dental caries: evaluation of the photosensitizers used and light source properties. Photodiagnosis and photodynamic therapy. 2022 Jun 1;9(2):122-31 . de Oliveira AB, Ferrisse TM, Marques RS, de Annunzio SR, Brighenti FL, Fontana CR. Effect of photodynamic therapy on microorganisms responsible for dental caries: A systematic review and meta-analysis. International journal of molecular sciences. 2023 Jan;20(14):3585. 50

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