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/cm2
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. 1. The photosensitiser only seeps a maximum of 2 cell
layers (=12µm) into the tissue
2. 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!
1. 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.
2. Pre-exposure: Rinse well!!!
A coating density of a hair‘s breadth leads to 95% absorption of
the light!
3. Exposure time per tooth / per cm2 min. 60sec., that
corresponds to approx. 3 J/cm2. An exposure time of > 120sec.
Should not be exceeded however.
4. 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 PLCE6 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 CE6 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 alone1,2
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/cm2 with CE6
• 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.

49. 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.

50. •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.

51. 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

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

53. 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.

54. • 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.

55. 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.

56. THANK YOU!