This document provides an overview of local drug delivery (LDD) systems for treating periodontitis. It discusses the history and rationale for LDD, including how it can achieve higher drug concentrations in periodontal pockets than systemic treatments. Ideal requirements for LDD like reaching the target site and maintaining adequate concentration for sufficient time are explained. Various types of LDD systems are classified and described, such as fibers, strips, gels, microparticles and nanoparticles. Specific examples of products using different agents are provided. The document concludes that LDD can augment mechanical debridement for managing periodontitis.

1. Presented by:
Aysha Khatri
PG part II
Dept of periodontology

2. INDEX
 Introduction
 History
 Systemic antimicrobials
 Rationale
 Comparison of systemic and local drug delivery
 Ideal requisite for locally delivered drug
 Classification

3.  Indication – Contraindication
 Advantage - Disadvantage
 Type of delivery system
 Various agents
 Newer trends
 LDD available in india
 conclusion
INDEX

4. INTRODUCTION
 CHRONIC PERIODONTITIS is a bacterial infection.The focus of most
nonsurgical periodontal therapy, including mechanical therapy such as
scaling and root planing (SRP), is to combat infection.
 After a single periodontal debridement session,
1. Supragingival plaque microorganisms reappear within hours or days.
2. Subgingival microbiota may re-establish within 42-60 days.
3. Bacteria may recolonize tooth surfaces from reservoirs on the tongue, tonsils
and buccal mucosa.
 Therefore chemical antimicrobials will further suppress periodontal
pathogens and thereby augment the effects of SRP.

5.  Methods employed to convey antimicrobial agents into periodontal pockets
have included systemic administration or local application .
 LOCAL DRUG DELIVERY SYSTEMS(LDD) are means of applying drugs to a
restricted region of the body.
 It was in the year 1979, DR. MAX GOODSON et al first proposed the concept of
controlled delivery in the treatment of periodontitis.
 It includes
 Pocket irrigation with chemical solutions.
The placement of solid or semisolid drug-containing formulations into the
periodontal pocket.
 Principle behind LDD is that Gingival Crevicular Fluid contained within the
pocket serves as a leaching medium for the discharge of a drug from the solid
dosage form and for its dispersal throughout the pocket, making it a regular
spot for treatment with local release delivery system.

6. HISTORY
GOODSON et
al 1979 –
used hollow
tetracycline
fibres
D. Steinberg
et al (1990)
researched
chlorhexidine
as a LDD
NakagawaT
et al (1991)
used
minocycline
Ainamo et al
(1992)
studied 25%
metronidazole
gel
Stoller et al
(1998) studied
doxycycline
hyclate

7. SYSTEMIC ANTIMICROBIALS
 Drug concentrations of systemically
delivered antimicrobials in the GCF are less
than those achievable with controlled-
release local delivery.
 Drug that is transferred from the plasma
compartment to the GCF in the periodontal
pocket is quickly washed away by the GCF
flow .

8. SYSTEMIC ANTIMICROBIALS
 It was previously thought that systemically delivered tetracyclines
markedly concentrated drug in the GCF compared with plasma.(Pascal
1986,Gordon 1981)
 This hypothesis was not supported by later studies(Sakellary 2000)
 However systemic therapies, rather than locally delivered agents, should
be considered when there are multiple pocket sites for the sake of
convenience and to save costs.

9. RATIONALE OF LOCAL DELIVERY
To remove any residual infective inflammatory element still harboring in the
periodontal apparatus that are not reachable to mechanical removal by hand or
motorized instruments.
Localized therapy has received significant attention because
 Site‐specific pattern of destruction of periodontal infections
 Potential side effects of systemic antimicrobials and anti‐inflammatory agents
 Systemic administration of many medications results in marginally effective local
concentrations of free active drug.

10. • Comparison of various methods of administration on basis of criteria for
success are given below.
• Since local drug delivery can achieve the above requirements, it was
thought important to critically assess the ability of these treatment
methods to attain or maintain periodontal health.
Mouth
rinse
Subgingival
irrigation
Systemic
Delivery
Controlled
Delivery
Reaches site of disease activity Poor Good Good Good
Adequate Drug concentration Good Good Fair Good
Adequate duration of therapy Poor Poor Fair Good
Gary Greenstein and Alan Poison,The Role of Local Drug Delivery in the management of Periodontal Diseases: A Comprehensive Review,
J Periodontol 1998;69:507-520.

11. Niklaus P. LangAnd Jan Lindhe; Clinical Periodontology and Implant Dentistry; 6th
edition.

12. IDEAL REQUISITES
 According to Greenstein andTonetti, local application of pharmacological
agents must fulfill the following criteria:
1. It must reach the intended site of action( Delivery to the site)
2. It must remain at an adequate concentration,
3. It should last for a sufficient duration of time
Greenstein G,Tonetti M.The role of controlled drug delivery for periodontitis. The Research, Science andTherapy Committee
of the References American Academy of Periodontology. J Periodontl. 2000;71(1):125-40.

13. 1.DELIVERYTOTHE SITE
 Agents in mouth rinses and supragingival irrigation do not predictably
reach beyond 5 mm into the periodontal pocket.
 However solutions delivered intracrevicularly via cannula or other device
can project deep into periodontal pocket.

14. 2.ADEQUATE CONCENTRATION
 Because of highly organised bacteria in form of biofilm they may impair
diffusion of agent, higher concentration may required.
 Drug should have a dose higher than Minimal Inhibitory Concentration (MIC).
 Antimicrobial agents that exert bactericidal effects within a 5-minute time
period are preferable for sub- gingival irrigation.
 Iodine-0.25%-0.5%
 Chlorhexidine and stannous fluoride (0.5-2%)
 Metronidazole and amoxicillin required microbial contact times of 60 minutes
or more for bactericidal activity

15. 3.SUFFICIENT CONTACT TIME
 Drug kinetics should follow zero order to stay there for long time.
 It also dependent on mechanism of action of drug; bactericidal
chlorhexidine requires shorter time than bacteriostatic tetracycline.
 Gingival crevicular fluid flow into Periodontal pockets averages 20 µl
per hour thus total pocket fluid volume may turn over about 40
times an hour in a moderate-sized periodontal pocket (0.5 µl
volume),
 which is more frequent than the oral cavity salivary turnover rate
of about 28 times an hour .

16. SUBSTANTIVITY
 Substantivity refers to property of a substance to bind to soft and/ or hard tissue
of the pocket, thereby establishing a drug reservoir.
 Balance between free drug and bound drug established and half life of drug
becomes prolonged.
 Incorporation of drug into various vehicles or devices, prior to placement into
periodontal pocket enhances substantivity.
 Chlorhexidine is first in having this property in dentistry, but in subgingival
environment tetracycline and clindamycin also have this effect.
 Influenced by a series of parameters like:
 Concentration of the medication, Length of time of contact of the solution with the oral
structures, pH,Temperature.
Goodson J. Pharmacokinetic principles controlling efficacy of oral therapy. J Dent Res 1989;68: 1625- 32.
Greenstein G,Tonetti M. Academy report:The role of controlled drug delivery for periodontitis(Position paper).J Periodontol 2000;71:125-40.

17. CLASSIFICATION
[Rams and Slots] 1996
Home oral irrigation
Home oral irrigation jet tips
Traditional jet tips
Oral irrigation (water pick)
Soft cone rubber tips (pick
pocket)
Nonsustained
Nonsustained
Sustained
Professional pocket irrigation
Controlled release devices
Hollow fibres
Dialysis tubing
Fibers
Gels
microspheres

18. Based onTHE DURATION OF MEDICAMENT RELEASE
(Greenstein andTonetti 2000)
Designed to
provide drug
delivery for less
than 24 hours
Sustained
release
devices
Designed to provide
drug release that at
least exceeds 1 day
or for at least 3 days
following application
Controlled
release
devices
DEPENDING ON
DEGRADABILITY
1.Nondegradable
devices (first
generation)
2.Degradable
devices (second
generation

19. INDICATIONS
 Isolated periodontal pockets (>5mm), with successful phase I therapy.
 Periodontal patients who are medically compromised where surgical
therapy is contraindicated.
 In combination with mechanical debridement or alone.
 In patients who are suffering from recurrent or refractory periodontitis.
 The patient is on supportive periodontal treatment.

20. CONTRA-INDICATIONS:
1. Patients with hypersensitivity to the drug.
2. Patients susceptible to infective endocarditis in order to reduce risk of
bacteremia.
3. Use of ultrasonic device based drug delivery system is contraindicated in
asthmatics, patients with cardiac pacemakers, AIDS and tuberculosis.
4. Pregnant or Lactating patients if drug shows harmful effects.
5. In aggressive form of periodontal disease where systemic antibiotics is
more effective.

21. ADVANTAGE
 A local route of drug delivery can attain 100-fold higher concentrations of an
antimicrobial agent in subgingival sites compared with a systemic drug regimen.
 Local delivery may employ antimicrobial agents not suitable for systemic
administration such as various broad spectrum antiseptic solutions e.g.
chlorhexidine.
 Personally applied antimicrobial regimens offer the potential of daily placement
into pockets, for compliant patients.
 Professionally applied antimicrobial regimens reduce potential problems with
patient compliance.
 Reduces the dangers associated with systemic administration such as toxicity,
adverse reactions, resistant strains and superimposed infections.
 It decreases risk for promoting microbial resistance.

22. DISADVANTAGES
 Difficulty in placing antimicrobial agents into deeper parts of pockets and
furcation lesions.
 Patient compliance and manual dexterity.
 Time consuming in patients with numerous advanced lesions.
 Do not markedly affect pathogens residing on other oral surfaces.
 Non-sustained drug delivery provides only a brief exposure of the target
microorganism to the applied antimicrobial agent

23. VARIOUS FORMS

24. In 1962,a Colorado dentist Gerald Moyer in
collaboration with an Engineer John Mattingly
introduced the Oral Irrigation system as an
alternative to dental flossing to enhance patients' oral
hygiene.
• Mechanism : Irrigation flushes away the bacteria.
• OI systems comprise two components, the device and the
irrigating solution.
 Mono-jet/multi-streamed jet tips are available for supra-
gingival irrigation, and blunt cannula with end or side
ports.
• Waterpik®, is one such OI device with a reservoir and a handle with replaceable tips.
• Studies have shown that Waterpik® is effective in removing the bacterial biofilm from
the crest of marginal gingiva at a moderate to high pressure setting of 50–90 psi and
pulsation rate of 1200–1400 per min.

25. • Several clinical studies
have been done till date
which showed better
therapeutic results as an
adjunctive therapy to SRP.
• Due to
 restricted penetration
into depth of pocket,
 lack of sustained release
of drug and
 rapid clearance by GCF
other systems are
developed.
• 0.2% chlorhexidine gluconate
• Saline solution
• Sterile water
• 10 mg/ml of tetracycline
• Povidone iodine (2–10%)
• Ozonated water
• 0.25% sodium hypochlorite
• Essential oils
• Mixture of 1% povidone and 3%
hydrogen peroxide
VARIOUS CHEMICALS USED in
ORAL IRRIGATION:

26. Fibers are reservoir type of therapeutic formulation
system that are placed circumferentially into the
periodontal pocket using an applicator and sealed
with a cyanoacrylate adhesive or a periodontal dressing.
Polymers used are:
A. Biodegradable:
1.Natural : Chitosan, Zein And Gelatin
2.Synthetic : poly (lactide-co-glycolide) (PLGA) or poly (caprolactone) (PCL)
B. Non-biodegradable : ethylene vinyl acetate(eva), cellulose acetate
e.g. Actisite(Tetracycline Fibre)

27. Strips and films (SF) are polymer based thin bands of
matrix system designed to deliver the active
therapeutic agents in a controlled and sustained
fashion when precisely placed in the interproximal
periodontal pocket space.
• A Japanese periodontist Noguchi, demonstrated the application of these systems in
the year 1984
• polymers used are
1. Biodegradable in nature such as polylactic acid, polyglycolic acid, poly-caprolactone
and poly hydroxyl butyric acid (PHBA) or
2. Non-biodegradable polymers such as ethyl cellulose, cellulose acetate, and ethyl
methacrylate etc .

28. • Several studies in literature have used combination of these polymers to
deliver antimicrobials such as doxycycline, tetracycline, metronidazole and
chlorhexidine.
• Results of these studies proved that Strips and Films loaded with drugs were
effective in reducing clinical variables such as plaque index, gingival index,
PPD scores and improved CAL with reduction in colony count of aa., Pg., And
fusobacterium species
• E.g. Periochip( Chlorhexidine)

29. Gels are dilute, cross-linked semisolid systems in which
liquid particles/ the active drug molecules are uniformly
dispersed in a solid medium that exhibits no flow when in
the steady-state
• Gels with active therapeutic agents are delivered by using wide port needle syringes to
ensure a uniform distribution throughout the diseased site.
• Gels are formulated using various polymers such as carbopol, xanthan, carboxy methyl
cellulose and Chitosan and are loaded with wide range of therapeutic agents such as
antimicrobials , bisphosphonates (alendronates , zoledronates) and statins
(simvastatin)
e.g.
1.5%chlorhexidine (Chlosite, a xanthan gum-based gel)
doxycycline hyclate (Atridox)
Minocycline HCL (2%) formulation(DENTOMYCIN/ PERIOCLINE).

30. VESICULAR SYSTEMS
 Vesicular liposomal systems are designed to
mimic the biomembranes in terms of structure
and bio behaviour, and hence are investigated
intensively for targeting periodontal biofilms.
 A lectin-bearing liposomes (proteoliposomes)
have been found to be effective for the delivery
of triclosan to periodontal biofilms.,The
potential of this system has been extensively
studied byVyas et al 2001.

31. MICROPARTICLES are solid spherical polymeric structures
with a diameter range of 1–1000 μm designed to contain
active therapeutic agents, dispersed uniformly throughout
the polymeric matrix.
• Several clinical studies have demonstrated the use of drug loaded microparticles for
application in periodontitis.
• Lycopene encapsulated solid lipid microparticles has shown positive clinical results
when it is used along with SRP.(M.S. Tawfik-2019)
• Doxycycline loaded biodegradable microspheres. (R.C. Mundargi-2007).
• Arestin™ is an USFDA approved PGLA based minocycline hydrochloride (1 mg/unit
dose cartridge) microsphere.(G.R. Persson-2006)

32.  The nanoparticulate system provides several advantages,
 Including high dispersibility in an aqueous medium
 Controlled release rate and
 Stability.
 Nanoparticles, owing to their small size, penetrate regions that may be
inaccessible to other delivery systems, such as the periodontal pocket areas
below the gum line.
The polymer-based nanoparticles were prepared via
micellar polymerisation, which resulted in a well
dispersible white powder material with particle size in the
range of 50–180 nm.

33. These systems
 Reduce the frequency of administration and
 Provide a uniform distribution of the active agent over an extended period of
time.
 Biocompatible nanoparticles composed of 2-hydroxyethyl methacrylate
(HEMA) and poly ethyleneglycol dimethacrylate (PEGDMA) could be used as a
drug delivery system for dental applications.
 Triclosan-loaded polymeric (PLGA, PLA and cellulose acetate phthalate)
nanoparticles were prepared by emulsification–diffusion process.
 A preliminary in vivo study in dogs with induced periodontal defects suggested
that triclosan-loaded nanoparticles penetrate through the junctional
epithelium (Pinon et al-2005)

34. VARIOUS DRUGS
Tetracycline Minocycline Doxycycline
Metronidazole Azithromycin Chlorhexidine
Other drugs like CLARITHROMYCIN,
ALENDRONATES,OFLOXACIN,
CLINDAMYCIN and other newer drug
delivery systems

35. TETRACYCLINE
 The first product introduced into the U.S. Market and most extensively tested in the early 1990
tetracycline‐releasing device is the ACTISITE periodontal fiber,it is no longer commercially
available.
 9-inch long ethylene or vinyl acetate copolymer fibre
 It is packed into the periodontal pocket, secured with a thin layer of cyanoacrylate adhesive, and
left in place for 7–12 days, continuous delivery of tetracycline maintains a local concentration of
1000 mg/L throughout that period(GOODSON et al. 1983, 1991).
 other studies which have assessed the effect of tetracycline in this vehicle.
 MINABE et al. 1991; JEONG et al. 1994; NEWMAN et al. 1994; DRISKO et al. 1995;TONETTI et al.
1998;WONG et al. 1998; KINANE & RADVAR 1999;YALCIN et al. 1999; AIMETTI et al. 2004
impregnated in 12.7-mg(25%)
tetracycline HCL

36. PERIOCOL-TC
 PerioCol-TC vial contains fish type I collagen (approximately 25 mg)
impregnated with approximately 2.0 mg of tetracycline hydrochloride,
which is sterilized by gamma radiation.
 PerioCol-TC releases tetracycline in vitro for 8 to 10 days.
 The fibers are moistened with saline and placed into the periodontal
pocket to the depth of the pocket base; they are biodegradable and do not
have to be removed.
 PerioCol-TC is stored in a dry place between 5° C (41° F) and 25° C (77° F)
and has a shelf life of 2 years with proper storage

37. PERIODONTAL PLUS AB
 Periodontal Plus AB is a bioresorbable tetracycline
fiber. It is 25 mg of pure fibrillar collagen evenly
impregnated with approximately 2mg of
tetracycline hydrochloride.
 The fiber biodegrades in the periodontal pocket
within 7 days.
 The fiber should be retained with a periodontal
dressing or covered with a dental adhesive for 10
days.

38. DOXYCYCLINE(ATRIDOX)
 Two-syringe mixing system.
 Syringe A contains 450 mg of a bioabsorbable polymeric formulation of 36.7% poly(D,L,-
lactide) dissolved in 63.3% N methyl- 2-pyrrolidone.
 Syringe B contains 50 mg of doxycycline hyclate, equivalent to 42.5 mg of doxycycline.
 When mixed, the product is a viscous liquid of 500 mg, which contains 50 mg (10%) of
doxycycline hyclate.
 The gel has been reported to release doxycycline in the GCF over 7 days, it is
biodegradable and does not require removal.
 If not used immediately, the mixed contents in syringe A can be stored in an airtight
container at room temperature for a maximum of 3 days.
 At least seven randomized clinical trials have tested this formulation
(Wennstrom et al. 2001; Eickholz et al. 2002; Akalin et al. 2004; Agan et al. 2006; Machion et al. 2006;
Bogren et al. 2008; Gupta et al. 2008).

39. LIGOSAN SLOW RELEASE
 Ligosan Slow Release is a 14% (w/w) resorbable doxycycline gel for periodontal
application provided in a laminate pouch and stored under refrigeration.
 The product is used by inserting the cartridge into the caulking gun, opening the
spray nozzle, and then discharging the gel to the bottom of the pocket.
 The doxycycline release profile was studied in 20 patients.(Heraeus Kulzer)
 The maximal value in the GCF within the first 5 hours, remained above 16 μg/mL
for at least 12 days.
 Mechanical hygiene in the area should be avoided for 7 days.

40. CHLORHEXIDINE
 Chip sized 4.0 × 5.0 × 0.35 mm
 2.5 mg of the active ingredient chlorhexidine gluconate.
 Matrix - hydrolyzed gelatin that is cross-linked with glutaraldehyde packaged in
individual foil containers.
 The chip releases chlorhexidine into the gingival crevicular fluid (GCF) over 7 to 10
days in pocket.
 The chip is biodegradable and does not require removal, but dental floss should be
avoided for 10 days to avoid dislodging it.
 It has been extensively tested in at least 11 trials
Soskolne et al. 1997; Jeffcoat et al. 1998, 2000;Heasman et al. 2001; Azmak et al. 2002; Grisi et al.
2002; Mizrak et al. 2006; Carvalho et al. 2007; Kasajet al. 2007; Paolantonio et al. 2008; Sakellari et al.
2010).

41. PERIOCOL-CG
 PerioCol-CG is a small, 10-mg chip (4 × 5 × 0.25–0.32 mm) designed as a collagen
matrix into which chlorhexidine gluconate (2.5 mg) is incorporated from a 20%
chlorhexidine solution that is its active ingredient.
 The chip is designed for insertion into the periodontal pocket and resorbs after
30 days, but its coronal edge degrades within 10 days.
 It releases chlorhexidine in vitro at a rate of approximately 40% to 45% in the
first 24 hours, followed by a linear release for 7 to 8 days, and it has a shelf life of
2 years.

42. CHLO-SITE
 Chlo-Site is a xanthan gel, consisting of a
saccharide polymer as a three-dimensional
mesh containing 1.5% chlorhexidine in 0.5
mL of gel, which is injected into the
periodontal pocket .
 The gel product is sterilized by gamma
radiation at 2.5 Mrad and is individually
packed for delivery in 0.25-mL prefilled
syringes fitted with a blunt side-exit needle
 This product has been tested in at least two
trials (Gupta et al. 2008; Paolantonio et al.
2009).

43. MINOCYCLINE
 Two forms are available:
1. 2% ointment (DAPTOMYCIN)
2. A powder consisting of resorbable polymer microspheres (ARESTIN).
Each cartridge delivers minocycline hydrochloride equivalent to 1 mg of
minocycline free base in Arestin.
 At least 13 randomized clinical trials have been done for Arestin.
(Nakagawa et al. 1991; van Steenberghe et al. 1993; Jones et al. 1994; Graca et al.
1997; Jarrold et al. 1997; Kinane & Radvar 1999;Williams et al. 2001; Henderson et al.
2002; Meinberg et al. 2002;Van Dyke et al. 2002; Goodson et al. 2007; Bland et al. 2010)

44. METRONIDAZOLE
 The most extensively used device for metronidazole application is a gel
consisting of a semi‐solid suspension of 25% METRONIDAZOLE benzoate
in a mixture of glyceryl mono‐oleate and sesame oil (ELYZOL).
 The gel is applied with a syringe into the pocket, and its viscosity should
increase after placement.
 Seven randomized clinical trials have evaluated the effects of this
formulation as an adjunct to non‐surgical mechanical therapy
 (Noyan et al. 1997; Lie et al. 1998; Kinane & Radvar 1999; Palmer et al.
1999; Riep et al. 1999; Griffiths et al. 2000; Stelzel & Flores‐de‐Jacoby
2000).

46. AZITHROMYCIN
 Azithromycin(AZM) is a semisynthetic, acid-stable antibiotic and represents the
prototype of a novel class of macrolides named azalides.
 0.5%Azithromycin gel with poly(lactic- co-glycolic acid) (PLGA) for direct
placement in the periodontal pocket has been studied by A R Pradeep et al in 2008
in comparison to SRP alone.
 Differences in PPD reduction were statistically significant and CAL gains were
significantly greater in the test than in the control group after 3 months.
A.R. Pradeep, S.Vidya Sagar, Clinical and Microbiologic Effects of Subgingivally Delivered 0.5% Azithromycin in theTreatment of Chronic
Periodontitis; J Periodontol 2008;79:2125-2135.

47. CLARITHROMYCIN
 Clarithromycin (CLM) is a classic macrolide that possesses a broad antimicrobial
spectrum, better bioavailability, favorable tissue distribution, and a low incidence of
adverse drug reactions.
 Gingival fibroblasts - 38-fold and oral epithelial cells- 3.3-fold concentrate higher level
than extracellular levels.
 Esha Agarwal et al 2012 have done RCT to evaluate efficacy of local drug delivery of
0.5% CLARITHROMYCIN GEL as an adjunct to SRP in the treatment of current
smokers with chronic periodontitis, have shown enhanced clinical outcome.
 Following 6 months all the clinical parameters such as probing pocket depth, clinical
attachment level for clarithromycin group demonstrated marked improvement.
 The drug is yet to be patented and under analysis.
Esha Agarwal, A.R. Pradeep, Efficacy of Local Drug Delivery of 0.5% Clarithromycin Gel as an Adjunct to Non-Surgical Periodontal Therapy in
theTreatment of Current Smokers With Chronic Periodontitis:A Randomized Controlled Clinical Trial; J Periodontol 2012;83:1155-1163

48. CLINDAMYCIN
 Clindamycin, a lincosamide antibiotic, has been under-recognized as an
antimicrobial agent for use in dentistry.
 A six-month study of using 2% CLINDAMYCIN GEL as an adjunctive
therapy to SRP in periodontal disease was done showing clinically
significant improvement in pocket depth and clinical attachment level.(Ana
pejčić et al 2015)
Ana Pejčić, Draginja Kojović,Therapeutic Efficacy of Clindamycin gel as an Adjunct to Scaling and Root Planing Therapy in Chronic
Periodontal Disease; Acta Clin Croat 2015; 54:46-51

49. OFLOXACIN
 Ofloxacin is a newly developed synthetic
pyridone carboxylic acid (PCA) derivative.
 Ofloxacin showed marked antibacterial activity
against Bacteroides species, Fusobacterium
species and Aa.
 Okade and co-workers-(1990) developed a new
sub gingival release delivery system (PT-01)
containing Ofloxacin for sub gingival therapy.
 The PT-01 was found to be effective in the
reduction of supra gingival plaque, reduction in
the plaque index, reduction in bleeding on
probing.

50. STATINS
 Statins, are a group of drugs, used primarily to treat hyperlipidemia and to
prevent cardiovascular diseases.
 Apart from that they have anti-inflammatory, antioxidative, antibacterial,
and immunomodulatory properties and anabolic effects on the bone thus
they have been presented as new potential candidates for periodontal
therapy.
 20 clinical trials studied evaluating efficacy of 1.2% Simvastatin, 1.2%
Atorvastatin and 1.2% rosuvastatin, in them 13 shown a significant Pocket
Depth reduction, Clinical Attachment level gain, and Intrabony defect fill in
healthy patients.
Catherine Petit et al, Contribution of Statins towards Periodontal Treatment: A Review; Hindawi Mediators of Inflammation Volume
2019, Article ID 6367402, 33 pages https://doi.org/10.1155/2019/6367402

51. METFORMIN
• Shown to stimulate osteoblasts and reduce alveolar bone loss.
• Efficacy of 0.5%, 1%, and 1.5% METFORMIN gel as a local drug delivery
system in adjunct to scaling and root planing for treatment of intrabony
defects.
• Significant increase in the PD reduction, CAL gain, and improved IBD depth
reduction
Pradeep AR, Rao NS, Naik SB, Kumari M. Efficacy ofVarying Concentrations of Subgingivally Delivered Metformin in theTreatment of
Chronic Periodontitis: A Randomized Controlled Clinical Trial. J Periodontol 2013;84:212-220.115

52. CHITOSANTRIPOLYPHOSPHATE (TPP)
 Chitosan is a natural polysaccharide that has become established as a material with
great potential for use in biomedical applications.
 Chitosan can be physically or chemically crosslinked to prepare
microspheres/nanoparticles, films and gels.
 Chitosan and poly vinyl alcohol PVA film was prepared that delivered antibacterial
agent ornidazole into gingival crevicular fluid.(Wang LC 2009)
 Dung et al used Antisense oligonucleotide- loaded Chitosan Tripolyphosphate
(TPP) nanoparticles and showed the sustained release of oligonucleotides which is
suitable for the local therapeutic application in periodontal diseases.
Pragati S, Ashok S, Kuldeep S. Recent advances in periodontal drug delivery systems. Int J Drug Del 2009; 1: 1-14
Darshan B Mundinamane et al; NewerTrends In Local Drug Delivery For Periodontal Problems – A Preview. Int. Journal of Contemporary DentistrAUGUST,
2011

53. HERBAL PRODUCTS
 Various herbal formulations like aloe vera, neem, tulsi, propolis, cocoa husk,
pomegranate, cranberry , etc. are being used widely these days. (Kukreja BJ,
DodwadV 2012, Bansal S 2012)
 These products have shown promising results with no side effects and are
economical as well.
 The antimicrobial effects of green tea catechins on periodontopathogens have
been studied by Hirasawa et al (2002),they showed bactericidal activity against
black pigmented organism at a minimum inhibitory concentration (MIC) of 1
mg/ml.
 Kudva P et al (2011) also demonstrated clinical and microbiological
improvements following the use of Green tea catechin chip as an adjunct to
scaling and root planning.

54. PERIOCEUTICS
 Heska Corporation first introduced the term PERIOCEUTIC which is
combination of terms periodontal and therapeutic which includes
antimicrobial and host modulatory therapy in the management of
periodontal disease along with mechanical debridement

55. FLURBIPROFEN
 The ability of the non-steroidal anti-inflammatory drugs (NSAIDS) to block
cyclooxygenase pathway and reduce the prostaglandin synthesis led to series of
studies demonstrating inhibition of periodontal disease progression.
 Yewey et al., (1991) used flurbiprofen in beagles in form of biodegradable subgingival
delivery system shows positive outcome.
 N. C. Deshpande et al in 2013 studied 51 patients with localized periodontal pockets to
evaluate the efficacy of novel indigenously designed flurbiprofen controlled release
biodegradable gel system,0.3% FLURBIPROFEN in the Poly (lactide)-co-glycolide
copolymer (75:25 ratio) was used.
 The results of the study suggested the statistically significant (P < 0.05) improvement in
the gingival status of the patients on 14th day after placement.
Neeraj C. Deshpande, K. M. Bhat, Randomized, controlled clinical study to evaluate efficacy of novel indigenously designed controlled release
flurbiprofen gel system for management of periodontal diseases Contemporary Clinical Dentistry | Jan-Mar 2013 |Vol 4 | Issue 1

56. ALENDRONATE
 Alendronate (ALN), an amino bisphosphonate, is known to inhibit
osteoclastic bone resorption and was proposed to have osteostimulative
properties in vivo and in vitro as shown by an increase in matrix formation.
 Local delivery of 1% ALENDRONATE into the periodontal pocket
stimulated a significant increase in PD reduction, CAL gain, and improved
bone fill compared to a placebo gel as an adjunct to SRP.
Sharma A, Pradeep AR. Clinical efficacy of 1% alendronate gel as a local drug delivery system in the treatment of chronic
periodontitis: a randomized, controlled clinical trial. J Periodontol. 2012 Jan;83(1):11-8.

57. LDD AVAILABLE IN INDIA
DRUG PRIZE
PERIODONTAL PLUS AB
(tetracycline fibre)
885/- FOR 4 vials of 25mg
PERIOCOLTC(TETRACYCLINE
FIBRE) by eucare
480-580/-
PERIOCOL-CG ( chlorhexidine chip) 720-750/-

58. CONCLUSION
 Thorough SRP is highly effective in the treatment of chronic periodontitis
and is the standard approach to non-surgical periodontal therapy.
Clinicians may consider the use of LDDs in chronic periodontitis patients as
an adjunct to SRP.(AAP consensus).
 The sites most likely to be responsive to this adjunctive treatment method
may be refractory or recurrent periodontitis.
 At present, there are insufficient data to indicate that one local drug
delivery service is clearly superior to all the other systems.

59. REFERENCES
 Michael g. Newman , Fermin a. Carranza ;Newman and Carranza’s Clinical
Periodontology, 13th Edition,2019.
 Niklaus P. Lang And Jan Lindhe; Clinical Periodontology and Implant Dentistry; 6th
edition.
 Thomaes. Rams & Jorgen Slots, Local delivery of antimicrobial agents in the
periodontal pocket; PeriodontoIogy 2000,Vol. 10, 1996, 139-159
 Gary Greenstein andAlan Poison,The Role of Local Drug Delivery in the
management of Periodontal Diseases: A Comprehensive Review, J Periodontol
1998;69:507-520.
 Rajeshwari H.R., Dinesh Dhamecha, Local drug delivery systems in the
management of periodontitis: A scientific review; Journal of Controlled Release 307
(2019) 393–409
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.

60.  Rajeshwari H.R., Dinesh Dhamecha, Local drug delivery systems in the management of
periodontitis: A scientific review; Journal of Controlled Release 307 (2019) 393–409.
 Kukreja BJ, DodwadV. Herbal Mouthwashes – A Gift Of Nature: Int J Pharm Bio Sci 2012; 3:
46-52.
 Hirasawa, M.,Takada, K., Makimura, M. and Otake, S., 2002. Improvement of periodontal
status by green tea catechin using a local delivery system: a clinical pilot study. Journal of
periodontal research, 37(6), pp.433-438.
 Rajeev Arunachalam,Vini Rajeev,Perioceutics in the management of Periodontal Disease;J
Young Pharm, 2017; 9(1): 8-13.
 Greenstein G,Tonetti M. Academy report:The role of controlled drug delivery for
periodontitis (Position paper). J.Periodontol. 2000; 71: 125-140.
 Goodson J. Pharmacokinetic principles controlling efficacy of oral therapy. J Dent Res
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