Periodontics

1. LOCAL DRUG DELIVERY
Dr. R. Dhivya .,MDS

2. Contents
 Introduction
 Systemic Vs Local Drug Delivery
 Historical perspective
 Terminology and Objectives
 Indications and Contraindications
 Advantages and Disadvantages
 Ideal Requirements
 Classification of local antimicrobial therapy
 Irrigation System
 Carrier/Vehicle System
 Commercially available Systems
 Impact on Deep Probing Depths
 Inhibition of Periodontal Disease progression
 Impact of Local drug delivery on furcations
 Repair of Osseous Defects
 Future trends
 Conclusion
 References

3.  Periodontitis has multifactorial aetiology with the primary aetiologic
agents being pathogenic bacteria that reside in the subgingival area and
possess potent mechanisms of damaging host defences.
 Inflammatory responses triggered in response to periodontal pathogens
are the major events responsible for periodontal destruction
 Treatment of periodontal disease is directed towards the suppression
/elimination of subgingival microflora. Root debridement performed by
mechanical means, i.e., scaling and root planing (SRP), is the most
commonly used initial treatment approach
Introduction

4.  Unfavorable Anatomy Of The Tooth
 Presence Of Tissue Invasive Organisms
 Bacterial Invasion Into Dentinal Tubules
- Quirynen Et Al (2002)
Limitations of mechanical debridement
To overcome this, Antimicrobials both systemic and locally acting were used as
adjuncts to mechanical therapy

5.  Systemic antimicrobial agents may reduce or eliminate bacteria that
cannot be removed by scaling and root planning.
 Adverse effects limit the use of systemic antimicrobials
- (Golomb G. et al 1984)
Drug
Toxicity
Drug
Interaction
Acquired
Bacterial
Resistance
Patient’s
Compliance
Limiting the Drug to its
target Site
Achieve high concentration at target
site
Dr. Max Goodson in 1979 that championed and developed local delivery of therapeutic agents
into a viable concept.
Local delivery of antibacterial agents into periodontal pocket

6. ISSUE SYSTEMIC LOCAL
Route of administration Oral/ parentral Site specific
Drug distribution Wide distribution Narrow range
Therapeutic potential May reach widely
distributed micro
organisms better
May act better locally on
biofilm associated bacteria
Problem Systemic side effects Reinfection from nontreated
sites
Clinical Limitations Requires good patient
compliance
Reinfections limited to the
treated site
Drug Dosage Higher drug dosage
(mg)
Lower Dosage
Systemic Vs Local Drug Delivery

7. Peaklevels Few hours in plasma Within few minutes in GCF
Frequency Once in 6-12 hrs Once a week
Super infection Present Limited
Microbial resistance Present Limited
Time required Less time Longer if many sites are
treated

8. Initial efforts… flushing with antimicrobial agents….W.D. Miller .. 1880’s .. the use of
an antimicrobial mouthrinse (Listerine) to aid in fighting what was then known as
‘Pyorrhea alveolaris’.
The concept.. origin in the 1970’s based on the theory… if one could substantially
improve the cellular specificity of a drug there would be an accompanying significant
improvement in the therapeutic index;
Dr. Max GoodSon - 1979… championed and developed controlled release local
delivery of therapeutic agents…
Historical Perspective

9. Terminology
Antimicrobial agents : They are chemotherapeutic agents that reduce the amount of bacteria present either
by superficially targeting certain organisms or by nonspecifically reducing all bacteria.
Targeted drug delivery: refers to delivery of medication to a patient in a manner that increases
the concentration of the medication in some parts of the body relative to others.
Local delivery of antimicrobial agents in periodontics : Implies antimicrobial therapy placed directly
in the subgingival region. The term local delivery is usually used to suggest more specific or
targeted delivery of an agent.
Non-sustained subgingival drug delivery : Provides high pocket concentrations of the antimicrobial agent for
onlyshort time periods.
Sustained subgingival drug delivery/ Controlled release delivery (CRD) : CRD’s are designed to release a
drug slowly and to retain therapeutic level for a prolonged period of time.
Controlled release local delivery: Implies release of chemotherapeutic agents into the periodontal pockets
over an extended period of time, provides prolonged drug availability, and sustained drug action.
7

10. Objective
1
The use of a local antimicrobial is to prevent or control microbial induced inflammation
in an effective concentration and be maintained there long enough for the desired effect to
be accomplished without causing any side effects.

11. Advantages
- Local drug delivery can attain 100 folds higher concentrations of the 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.
- Local antimicrobial delivery reduces the dangers associate with systemic administration such as toxicity,adverse
reactions, resistant strains and superimposed infections.
1

12. 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.

13. Isolated
periodontal
pockets (>5mm),
with successful
phase 1 therapy
Periodontal
patients who are
medically
compromised
where surgical
therapy is
contraindicated.
In combination
with
mechanical
debridement
Patients who
are suffering
from recurrent
periodontitis.
During
periodontal
regenerative
procedures.
Indications

14. Patients with known
hypersensitivity
reaction to
antimicrobials
Those requiring
multiple areas of
treatment.
With local delivery
of Metronidazole
preparations,
contraindicated in
alcoholics.
Patients with
asthmatics, infective
conditions (AIDS,
TB) and pts with
Cardiac pacemakers
Contraindications

15. Ideal requirements for local antimicrobial agents
15
• Must deliver the drug to the base of pocket.
• Must have microbiologically effective concentrations in the pocket.
• Should sustain the concentration of the drug in the pocket for sufficient period of time & at a
concentration to be clinically effective.
• Less undesirable side effects
• No emergence of bacterial resistance
• Should be effective only against periodontal pathogens and not on commensal microflora.
• Cost-effectiveness and patient compliance . - (Goodson 1985)

16. Classification of local antimicrobial therapy
1.LANGER AND PEPPAS (1988) - Based on their mechanism of action
2. KORNMAN (1992) - Based on the rate controlling system
3.RAMS AND SLOTS (1996) - Depending on usage
4. SOSKOLNE (1997) - Based on physical form
5. GREENSTEIN & TONETTI (2000) - Based on duration of action

17. 1.LANGER AND PEPPAS (1988) - Based on their mechanism of action
I. Diffusion controlled systems
A. Reservoirs (membrane devices)
B. Matrices (monolithic device)
II. Chemically controlled systems
A. Bio-erodible systems
B. Pendant chain systems
III. Solvent activated Systems
A. Osmotic System
B. Swelling controlled systems
IV. Release induced by external forces
A. Magnetically controlled systems
Diffusion controlled
system
Dissolution
controlled system
Chemical controlled
systems
Solvent activated
systems
MECHANISMS

18. I . Diffusion controlled systems

19. II. Chemically controlled systems

20. III. Solvent activated Systems
Solvent activated System
- Osmotic system / Swelling
controlled system

21. IV. Release induced by external forces
Magnetically controlled systems

22. 2.KORNMAN (1992) - Based on the rate controlling system
Reservoir devices without rate controlling system
Reservoir devices with rate controlling system
Includes devices such as hollow fibers
filled with a therapeutic agent in which
the agent is released simply by
diffusion through the reservoir wall.
The most common forms include
solvent action on coated drug particles,
microporous polymer membranes or
monolithic matrices, or erodable
polymeric matrices.

23. 3.RAMS AND SLOTS (1996) - Depending on usage
PERSONALLYAPPLIED
(In patient home self-care)
PROFESSIONALLY APPLIED
(In dental office)
NON-SUSTAINED SUBGINGIVAL DRUG
DELIVERY
SUSTAINED SUBGINGIVAL DRUG
DELIVERY

24. 4. SOSKOLNE (1997) - Based on physical form
FIBRES
Hollow
Monofilament
Tetracycline
Chlorhexidine
FILMS
Matrix delivery systems
Biodegradable –
Soluble films
Fish collagen
Steinberg et al
Non biodegradable –
Insoluble films
Ethyl cellulose
CHX, tetracyclines,
metronidazole
INJECTABLE
SYSTEMS
Easy & effective
Cost saving
GELS
Solid/semisolid
formulations
Base – Methyl cellulose
CHX, metronidazole,
tetracycline etc

25. STRIPS &
COMPACTS
Polymers and
monomers
impregnated with
drug
Metronidazole, CHX,
Tetracycline,
Doxycycline
VESICULAR
SYSTEMS
Mimic biomembranes
Triclosan, CHX
MICROPARTICLE
SYSTEM
Biodegradable PLA
or PGLA
Minocycline
microspheres
NANOPARTICULATE
SYSTEM
Targeted controlled slow
drug release
Bioadhesive & increases
stability
Nano CHX

26. 5. GREENSTEIN & TONETTI (2000) - Based on duration of action
A) SUSTAINED RELEASE DEVICES
Drug delivery for less than 24 hrs require multiple applications
B) CONTROLLED DELIVERY DEVICES
Duration of drug release exceeds 24hrs administered once

27. Irrigation Methods
• Purpose of irrigation is to nonspecifically reduce the bacteria and their by-products that lead to the initiation
or progression of periodontal diseases.
• Supragingival irrigation allows for the disruption and dilution of marginal bacteria and their by-products
which helps to prevent or treat gingivitis.
• Subgingival irrigation interferes with the complex ecosystem required for the initiation and continued
destruction of the compromised periodontium in the susceptible host.
• Irrigation provides greater access of medicaments to periodontal pocket when compared to mouth rinsing
• Antiseptics in mouth rinses exert no direct effects on the subgingival microbiota due to nearly lack of
penetration of oral rinses below the gingival margin
• A variety of irrigator tips including cannulas and soft hollow rubber tips have been developed and modified for
home or professional use with irrigation delivery systems

28. IRRIGATION
Home Irrigation Professional Subgingival
Irrigation
Supra gingival Sub gingival Marginal

29. Home Irrigation Devices
• Home irrigation devices allow patient to deliver medicament into the periodontal pocket at home on a more
frequent basis than is practical with professional subgingival irrigation
• They show improved therapeutic efficacy with use of an antimicrobial solution
• Presently all home care methods offer only non sustained pocket delivery of antimicrobial agents
It is classified as :
- Supra gingival Irrigation
- Subgingival Irrigation
- Marginal Irrigation

30. Supragingival Home Irrigation
• Several studies have shown that water or other antimicrobial medicaments provide an
increased reduction of gingivitis and bleeding on probing (BOP) over normal oral hygiene
alone in maintenance patients
• Supragingival home irrigation will deliver medicaments only to about one half the depth of a
deeper periodontal pocket, therefore less useful in delivering medicaments in patients with
deeper pockets

31. Subgingival Home Irrigation
• A wide array of subgingival irrigation devices have been used in patient applied home irrigation.
• Patients seem to comply with recommendations to use home jet irrigators and find them relatively easy to
use .
• Macaulay and Newman had patients use a pulsed mono-jet subgingival irrigation system, once daily for 4
weeks and found the treatment to be effective in controlling subgingival plaque for at least 2 months after
the end of a 1- month period of active treatment.
• It appears that both supra and subgingival home irrigation is effective
• While supragingival irrigation can be performed by patients with a moderate degree of success,
subgingival irrigation in particular may pose technical difficulties for patients with limited dexterity

32. Limitations Of Subgingival Home Irrigation Devices
1. Inability of most patients to precisely place irrigation cannulas into subgingival sites
particularly in posterior interproximal areas
2. In case of patients with limited dexterity the use of home irrigation devices are difficult
3. More risk of injury if the tip is inserted incorrectly

33. Marginal Home Irrigation
• Marginal home irrigation is a hybrid of both supragingival and subgingival irrigation.
• This technique uses devices that have a traditional jet tip attachment that has been modified so that it can
deliver fluids subgingivally.
• Home marginal irrigation allows penetration of fluid to 90% of the depths of pockets 6mm deep or less deep
and to 64% of the depth of pockets 7mm deep or more.
• Antimicrobial home irrigation regimens provide little or no improvement in periodontal attachment level in the
absence of mechanical root debridement
• Thus, these approaches are best used in periodontitis treatment as adjuncts to professionally delivered
periodontal therapy, particularly during periodontal maintenance care

34. Professional irrigation
Two different systems;
• Direct irrigation using a hand-held syringe or mechanical irrigation using a
special pumping device that produces a stream of irrigant with regular
intermittent breaks resulting in a pulsating effect.
• Boyd et al (1992) evaluated subgingival irrigation using a pulsed jet irrigator
with either a standard tip or a cannula on an oral irrigator and found that
irrigation with the cannula tip penetrated farther into both medium (3.5 to 6.0
mm) and deep (> 6 mm) pockets than did irrigation with the standard
pulsating tip.
• Ultrasonic devices has been used to professionally deliver antimicrobial
agents into periodontal pockets during mechanical root debridement
procedures
• Irrigant delivered through ultrasonic scaling tips has shown complete pocket
penetration in 86% of sites ranging from 3-9mm depth

35. Agents Used For Sub- Gingival Irrigation
• bis-biguanide antiseptic
Chlorhexidine
• Symmetric molecule with four chlorophenyl rings and
two biguanide groups connected by a central
hexamethylene bridge.
Structure
• Di-cationic, above pH 3.5. Cationic nature- responsible
for efficacy, safety, local side effects.
• Broad spectrum
Properties

36. MOA - binds strongly to bacterial cell membrane.
At low concn-
- Binds to PO4 groups in LPS and COOH groups in
proteins- interferes with membrane transport.
- Increased permeability with leakage of intracellular
components
- (Hugo & Longworth 1964, 1965).
At high concn-
- Precipitation of bacterial cytoplasm and cell death
- (Hugo & Longworth 1966).

37. Keyes technique
• Consists of packing a mixture of NaCl, NaHCo3, H2O2 (3%) subgingivally and then
irrigating with an antiseptic solution such as povidone- iodine (0.5%).
• Used in combination with scaling, this has been reported to improve marginally the clinically
effects of SRP alone (Rosling et al 1983).

38. • Subgingival irrigation with 0.5% sodium hypochlorite
(Dakin’s solution) caused significantly greater and longer
lasting reduction in plaque and gingivitis than irrigation with
water.
Lobene et al 1972
• In localized juvenile periodontitis lesions, gingival curettage
with dilute sodium hypochlorite irrigation caused greater
reduction in proportions of subgingival spirochetes than water
irrigation
• Showed histologically that subgingival application of sodium
hypochlorite solution provide chemolysis of the soft tissue
wall of a periodontal pocket with minimal effect upon
adjacent tissues.
Adcock et al 1983
Kalkwarf et al 1982

39. American Dental
Association. Accepted
Dental Therapeutics. 1984
• The American Dental Association Council on Dental
Therapeutics proposed using dilute sodium hypochlorite as
a topical antiseptic, for irrigation of wounds and
as a mouthrinse
Perova et al 1990
• Sodium hypochlorite application improve periodontal
histological healing

40. Summary of professional irrigation studies
• Few anti-microbials professionally applied with non- sustained pocket delivery show significant
clinical benefits.
• Iodine,Sodium bicarbonate and sodium hypochlorite have been shown to be more effective than
other anti-microbial agents when used in conjunction with SRP.
• Iodine + polyvinyl pyrrolidone- Bactericidal effects against A. actinomycetemcomitans,
P.gingivalis, P.intermedia, F.nucleatum (Higashitsutsumi et al 1993).
• Iodine- irrigation attains bactericidal concn of 0.25-0.50% in the pocket (Caufield et al 1987).

41. Various Drug Delivery Devices
 Fibres
 Films
 Injectable Gels
 Strips And Compacts
 Vesicular Liposomal Systems
 Microparticle System
 Nanoparticle System

42. Fibers
• Fibers, or thread-like devices, are reservoir-type systems, placed circumferentially into the pockets with an
applicator and secured with an adhesive for the sustained release of the trapped drug into the periodontal
pocket.
• 2 types..
• Hollow - reserviours without rate control system- drug release--- diffusion.
Eg: tetracycline in hollow fibres of cellulose acetate. (1979)
• Monolithic- controlled dug release.
-- monolithic fibres of EVA with 25% tetracycline HCl.
Several polymers… Polyethylene, Polypropylene, Polycaprolactone, Polyurethane, Cellulose acetate propionate
and Ethylene vinyl acetate (EVA) have been investigated as matrices for LDD.
Eg: Chlorhexidine fibres, tetracycline fibres.

43. Films
• Films are matrix delivery systems in which drugs are distributed throughout the polymer and release
occurs by drug diffusion and/or matrix dissolution or erosion.
• Bigger films could be applied within the cavity onto the cheek mucosa or gingival surface

44. Both degradable and non- degradable films are
available.
Adva
ntag
es-
• Could be cut or punched into appropriate sizes so as to be inserted into the site of action.
• Can be easily inserted
• Minimal discomfort to the patient
• Sufficient adhesiveness is present
Non degradable films -- Addy et al., (1982) described the film or slab form intrapocket
delivery devices. They described the use of slabs of – made of methyl methacrylate for
the intrapocket delivery of tetracycline, metronidazole, chlorhexidine .
Degradable devices -- Periochip -- controlled subgingival delivery of chlorhexidine.

45. Injectable System
• It is relatively simple procedure.
• Fluid nature of the formulations would allow the drug to gain
access to the entire pocket.
• The application can be easily and rapidly carried out, without pain,
by using a syringe.
• The formulation undergo a change in to a sticky semisolid or solid
phase so as to prevent it from being washed out.

46. • A higher biocompatibility andbioadhesivity, allowing adhesion to the
mucosa in the dental pocket.
• They can be rapidly eliminated through normal
catabolic pathways, decreasing the risk of irritative or allergic host
reactions at the application site.
• Eg: gel formulations of tetracycline (2.5%), metronidazole (25%),
metronidazole benzoate (40%), combination of tetracycline (2.5%) and
metronidazole benzoate (40%).

47. Strips and Compacts
• Acrylic strips have been fabricated using a mixture of polymers,
monomers and different concentrations of antimicrobial agents.
• Strips containing tetracycline, metronidazole or chlorhexidine
demonstrated a decrease in number of motile rods, notably
spirochetes.
• In a later development, the evaluation of amoxycillin clavulanic acid
loaded acrylic strips is reported.

48. • Highest level of antibacterial agent was released during the first 24 hours period
followed by release of therapeutic level of drugs for a subsequent 9 days period.
• Effect persisted even after 3 week of removal of acrylic strips.
• Tissue adhesive implants were made using n-butyl-2-cyanoacrylate as a drug trapping
material and slowly release drug when used in the form of a biodegradable local drug
delivery device.

49. Vesicular Systems
• Designed to mimic the bio membranes in terms of structure and
biobehaviour, and hence are investigated intensively for targeting
periodontal biofilms.
• The targeting of liposomes was thought to be
because of the interactionof the polyhydroxy groups of liposomes with
surface polymers of the bacterial glycol-calyx.
• Proteoliposomes (Succinylated Concanavalin-A (lectin)-bearing liposomes)have
been found to be effective for the delivery of triclosan to periodontal
biofilms.
• Studies.. Even after a very short exposure, liposomes were retained in the
bacteria delivering the drug into cellular interiors. (Robinson et al.)

50. Microparticle System
• Non-biodegradable and biodegradable materials for the preparation of microspheres
include the polymers of natural origin, modified natural substances and synthetic
polymers.
• Biodegradable polymers such as poly lactide (PLA) or poly (lactide – co-glycolide)
PLGA has been designed for periodontal disease therapy.
• PLGA microspheres containing minocycline … have been used for the
elimination of Porphyromonas gingivalis from the periodontal pocket and provide
stability to the encapsulated drug.
• The in vitro drug release in these systems depends upon the polymer (lactide:glycolide)
ratio, molecular weight, crystallinity and pH of the medium

51. Nanoparticle System
• The nanoparticulate system provides several advantages as compared with microspheres,
microparticles and emulsion-based delivery systems, including high dispersibility in an
aqueous medium, controlled release rate and increased stability.
• Penetrate regions that may be inaccessible to other delivery systems, such as the
periodontal pocket areas below the gum line

52. • Three preliminary studies -- assess the efficacy of nanoparticles in periodontal drug delivery.
a) 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. (Dung
et al - 2001)
b) An in vivo study in dogs with induced periodontal defects using Triclosan-loaded polymeric (PLGA, PLA and
cellulose acetate phthalate) nanoparticles and suggested that triclosan-loaded nanoparticles penetrate through
the junctional epithelium. (Pinon et al – 2005)
c) the in vitro bactericidal activity of the Harungana madagascariensis leaf extract (HLE) on the oral bacterial
strains largely implicated in dental caries and gingivitis infections. - Moulari et. Al – 2006

53. Commercially Available synthetic Products
• Tetracycline fibers (Actisite, Alza Corp., Mountain view, California)
• Minocycline ointment (Arestin , Dentomycine, Lederle, UK )
• Doxycycline hyclate in a resorbable polymer (Atridox, Atrix Labs, CO)
• Metronidazole gel (Elyzol, Metrogene ,Dumex, Copenhagen, Denmark)
• Chlorhexidine Chip (Perio chip Peno Products Ltd., Jerusalem, Israel)

54. Tetracycline
• Tetracycline is a bacteriostatic antibiotic that interferes with bacterial protein
synthesis and inhibits tissue collagenase activity.
• Agents used commonly are: Tetracycline HCl, Doxycycline HCl, Minocycline HCl
• Goodson et al in 1979 first proposed the concept of controlled delivery in the
treatment of periodontitis.
• The first delivery devices involved hollow fibers of cellulose acetate filled with
tetracycline.

55. Tetracycline –containing fibers (Actisite)
• FDA approved.
• Non resorbable, biologically inert, safe polymer (ethylene
vinyl acetate) loaded with 25%w/w tetracycline HCl powder.
• Packed as flexible yellow fibres of 0.5mm d, 23cm length (2.7 mg TTC).
• Maintains constant concentrations of active drug in the crevicular fluid in excess of 1000
μg/mL for 10 days. Maurizio S etal)
• In contrast GCF conc. of only 4-8 microgram/ml were reported after systemic administration,
250 mg qid for 10 days.

56. Placement Of Actisite Fiber

57. • In a 60-day multicenter study - 107 periodontitis patients after supragingival scaling,…
• Four non-adjacent te.eth (pockets in the range of 6-10mm) was selected and randomly assigned
to 4 groups- Tetracycline fiber, Placebo fiber, Scaling and Untreated.
• Results-fiber therapy significantly had reduction in probing depth, BOP,and gain in
attachment levels. (Goodson et al- 1992 )
• … study in periodontal maintenance patients needing treatment of localized recurrent
periodontitis…Effect of fiber therapy was evaluated as an adjunct to SRP.
• Results – sites treated with fiber and SRP showed significantly higher attachment level, pocket
depth reduction and less BOP (Newman et al - 1994)

58. Other forms:
• Bioresorbable form is PERIODONTAL PLUS AB
• formulation containing TTC (2 mg of Tetracycline) in 25 mg of
collagen fibrils.
Dual mode of action by…...
• enablesthe active agent and vehicle to
be able to work positively
towards the repair of the periodontal lesion.
• Each vial contains 25 mg (Total 100 mg in 4 vials)

59. Tetracycline-Serratiopeptidase-Containing Periodontal Gel
• Study- - Serratiopeptidase tetra gel with aerosol (colloidal silica) used.
• …. Aimed to decrease polymer concentration and to obtain reasonable
vicocity at a lower concentration of pluronic gel by adding a viscocity
modifier.
• Results - Formulation has shown statistically significant results along with
scaling and root planing. ( Maheshwari et al )

60. Author LDD agent Results Conclusion
Singh et
al.(2009)
3 months
TTC impregnated
collagen fibres.
No difference in the results achieved
with local tetracycline
hydrochloride or local
metronidazole as adjuncts to
mechanotherapy
Both resulted in greater
antibiotic therapies
improvement in
microbiological
parameters when
compared to
mechanotherapy alone.
Sadaf et
al.(2012)
3months
.
Tetracycline
fibers-
Higher reduction in plaque index,
gingival index and in the clinical
probing depths of the tested group
than of the control group at all time
intervals -15, 30, 60 and 90 days.
Effective as adjunct to
SRP.
Gupta et
al.(2015)
TTC impregnated
collagen fibres.
more reduction in clinical
parameters (PD,GI, PI) compared
to control
Tetracycline fiber
therapy enhances the
benefits of SRP in the
treatment of chronic
periodontitis
STUDIES

61. Subgingival Doxycycline
• broad-spectrum antibiotic
• bacteriostatic, inhibiting bacterial protein synthesis
• ability to downregulate MMPs.
• The only FDA approved 10% Doxycycline – ATRIDOX gel (42.5 mg Doxycycline)
• Subgingival controlled-release product composed of a 2 syringe mixing system.

62. 49
• 2 syringe mixing system
• Syringe A -- 450 mg of the ATRIGEL® Delivery
System, which is a bioabsorbable, flowable
polymeric formulation.
• Syringe B- doxycycline hyclate which is equivalent to
42.5 mg doxycycline.

63. • The constituted product is a pale yellow to yellow viscous liquid with a concentration of 10% of
doxycycline hyclate.
Upon contact with the crevicular fluid, the liquid product solidifies and quickly hardens to a wax-
like substance, then allows for controlled release of drug for a period of 7 days.

64. Doxycycline levels in GCF Time
1,500 - 2000 μg/mL 2 hours
> 1000 μg/mL 18 hours
Well above the minimum inhibitory
concentration for
periodontal pathogens (6.0 μg/mL)
Day 7
95% of the polymer is bio absorbed or
expelled from the pocket
naturally
Day 28
(Polson AM, 1997

65. author Results and conclusion
Garrett ,2003 - Atridox was compared to
placebo control and oral
hygiene and SRP…. In 411
pts with moderate to severe
adult periodontitis.
Treatment to be statistically superior
to placebo control and oral hygiene
and equally effective as SRP.
Machion L et al. 2006.
evaluated the association of
locally delivered doxycycline
10% in the periodontal
treatment of smokers(2 yrs)
Reduction in clinical
parameters…use of locally
delivered doxycycline may constitute
an important adjunct for the active
and supportive treatments of severe
periodontal disease in smokers.
Deo et al.(2011)- Doxycycline hyclate 10% as
an adjunct to SRP (6 months)
-
significant reductions in PPD and
gains in CAL compared to SRP
alone.
studies

66. Subgingival Minocycline
• Semisynthetic tetracycline - first introduced in 1967
• in vitro antibacterial activity against a wide range of
gram-ve and gram+ve microorganisms
• LDD minocycline -- tried clinically via in three different modes i.e. film, microspheres,
and ointment.
1. Film:
• Ethyl cellulose film containing 30% of Minocycline were tested as sustained release
• complete eradication of pathogenic flora from the pocket after 14 days.

67. 2.Microsphere:
• Locally delivered, sustained release form of minocycline
microspheres (ARESTIN) for subgingival placement is
available.
• Arestin-- 2% minocycline encapsulated into bio-resorbable
microspheres (20-60μm in diameter) in a gel carrier and
has resorption time of 21 days.
• Gingival crevicular fluid hydrolyses the polymer and
releases minocycline for a period of 14 days or
longer before resorbing completely.

68. Electron photomicrograph and
CS view of microsphere showing
minocycline HCL particles
The microspheres is dispensed
subgingivally to the base of the
periodontal pocket by means
of disposable plastic cartridge
affixed to a stainless-steel handle
.

69. 3.Ointment:
• 2% minocycline hydrochloride in a matrix of hydroxyethyl-cellulose, aminoalkyl-methacrylate,
Triacetine & glycerine.
• DENTOMYCIN – European union
• PERIOCLINE - JAPAN
• The concentration of minocycline in the periodontal pocket is about 1300μg/ml, 1 hr after single topical
application of 0.05 ml ointment (1mg of minocycline) and is reduced to 90μg/ml after 7 hrs.
The Dentomycin gel has been reported to be effective in periodontal disease because of:
• Its power to eliminate key periodontal pathogens.
• Minimal risk of bacterial resistance.
• Inhibits harmful bacterial collagenase without effecting normal collagen turnover and regeneration of gingival
tissues.

70. author studies Results and conclusion
Van
Steenberghe
et al - 1993
–103 adults with moderate to severe periodontitis…
SRP
done at baseline
Patients received either the test or a control
minocycline ointment (dentomycin gel) in four
sessions at an interval of 4 weeks.
– a significantly greater reduction of PD in
test group- Treatment to be statistically
superior to control
Steenberghe et
al (1999)
Locally administered minocycline microspheres-–
multicenter trial -748 pts with moderate to
advanced periodontitis. -
combined therapy provided a better result
than SRP alone at sites >7 mm deep...
Results – test sites showed significantly
more PD reduction than either SRP alone.
Jung et al.(
2012)
Minocycline hydrochloride2% - Reductions in PPD, BOP and gain in CAL
were significantly greater at the
minocycline ointment in association with
flap surgery site than at the flap surgery
site alone.
Pandit N , et
al,2013)
A randomized, controlled, study.. to evaluate and
compare the efficacy of subgingivally delivered
Minocycline microspheres and 25% Metronidazole
gel when used as an adjunct to SRP
that treatment with Minocycline
microspheres and Metronidazole gel
improve PPD and CAL in patients with
periodontitis compared to SRP alone.

71. Subgingival Metronidazole
• Metronidazole is particularly attractive as an antimicrobial because of its selective
efficacy against obligate anaerobes.
• Both systemic and local applications are effective against periodontal pathogens.
• Metronidazole has been incorporated as collagen sponges, dialysis tubing, acrylic strips,
films and gel forms for sustained subgingival delivery in the treatment of periodontal
disease.

72. Elyzol
• metronidazole 25% in a mixture of glyceryl mono-oleate
and sesame oil.
• Contains metronidazole benzoate- active agent.
• It flows freely on application.. on contact with gingival
crevicular fluid, becomes more viscous and stays in the
periodontal pocket… gel disintegrates in the pocket and
releases metronidazole for at least 24 hours.
• Can be administered quickly and easily and high
periodontal pocket levels of metronidazole are
maintained.
• Administered twice- with an interval of one week.

73. Metrogene (Septodent, France)
• It is anew combinationof two known substances; bovine collagen (Type I) sponges into which
Metronidazole is incorporated at a concentration of 5 percent in the finished product.
• In contact with human gingival fluid, this collagen rapidly forms a resorbable gel which is
non-irritant as it is virtually devoid of any immunogenicity (Hugly 1983, Stein 1985).

74. author Studies Results and conclusion
Ainamo et al 1992 – two randomly selected quadrants were
treated with the gel twice a week; other
two – 2 episodes of subgingival scaling.
.
No significant differences.
. Pedrazolli et al 1992
(6- months)
microbiological outcome of 2 gel
applications vs scaling was compared.
total bacterial cultivable count and
proportions of anaerobic bacteria
were affected in a similar way in
both groups, and no difference was
seen in PD reduction & BOP.
Griffiths et al.(2000) -9 months-Metronidazole 25% dental gel. -Combined therapy of SRP and
metronidazole 25% dental gel was
superior to the conventional
treatment of SRP alone
STUDIES

75. Chlorhexidine
• Available as mouthrinses, Gels, varnishes, and chip to be used as a local drug delivery agent
MECHANISM OF ACTION (Rolla and Melsen)
• By binding to anionic acid groups on salivary glycoproteins thus reducing pellicle formation and plaque
colonization.
• By binding to salivary bacteria and interfering with their adsorption to teeth.
• Chlorhexidine has been shown to be an effective agent in plaque inhibition (Loe et al 1976)
as…well retained in the oral cavity,
• Reacting reversibly with receptors in the mouth due to its affinity for hydroxyapetite and acidic salivary
protein.
• Its antibacterial action is due to an increase of the cellular membrane permeability followed by the coagulation
of intracellular cytoplasmic macromolecule.

76. Periochip:
• small chip (4.5× 3.5mm) composed of biodegradable hydrolyzed gelatin matrix,
crosslinked with glutaraldehyde, also contains glycerine &water into which
chlorhexidine gluconate (2.5mg) is incorporated.
• Perio Chip releases chlorhexidine in vitro in a biphasic manner,
• Initially releasing approximately 40% of the chlorhexidine within the first 24 hours,
and then releasing the remaining chlorhexidine in an almost linear fashion for 7–
10 days.

77. • Unique patented “targeted
controlled release” bio degradable
polymer containing chlorhexidine.
• Small, bullet-shaped or baby’s
finger nail like thin film, weighing
7.4mg.

78. • Insertion of a chlorhexidine chip into a residual pocket mesial to an upper molar
with a furcation involvement.

79. Periocol-CG:
-Periocol CG is prepared by incorporating 2.5mg
chlorhexidine from a 20% chlorhexidine solution in
collagen membrane
- Size of the chip is 4x5 mm and thickness is
0.25 - 0.32 mm and 10 mg wt.

80. Chlosite application
Chlo-Site is an agent containing 1.5% chlorhexidine of
xanthan type .
•Xanthan gel is a saccharide polymer, which constitutes
of a three-dimensional mesh mechanism, which is
biocompatible with chlorhexidine.
Chlo-Site

81. author Results and conclusion
Soskolne et al
1997, Jeffcoat
et al 1998
split mouth design to compare the treatment
outcomes of SRP alone with the combined
use of SRP & PerioChip in pocket depth of
5-8mm.
– average PD reduction in treated sites with
chip was significantly greater than in the
sites receiving mechanical treatment only.
Grover et al.(2011)
3 months -Chlorhexidine chip and SRP. .
resulted in a clinically significant
improvement
in PPD and CAL compared with SRP alone.
Medaiah et
al.(2014 - 3 months-Biodegradable chlorhexidine chip-
No statistically significant differences
between SRP and SRP + CHIP group in all
clinical parameters
STUDIES

82. STUDIES
• Meta-analysis on four studies including SRP and local sustained release agents
compared with SRP alone….
Results …when SRP is combined with certain antiinfective agents in sustained release
vehicles, statistically significant adjunctive effects on PD reduction and a decreased
percentage of sites with BOP can be anticipated. Statistically significant effects of PD
reduction were seen with CHX chip.
• Compared with SRP alone, no evidence was found for the adjunctive effects on reduction
of PI with ATRIDOX and MINO microspheres. BOP reductions were not significant with
ATRIDOX and TET fibres.
• large effect of adjunctive therapy in pocket depth reduction, with a moderate effect on
reduction of bleeding scores and mild effect on reduction of plaque scores.

83. Newer Trends In Local Drug Delivery
• A novel bisphosphonate; very potent inhibitor of bone resorption.Alendronate (ALN), an
aminobisphosphonate, 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% ALN into periodontal pockets as
an adjunct to SRP stimulated a significant increase in PD
reduction, CAL gain, and improved bone fill.
-(Anuj Sharma et al - 2011)
•Veena et al -2010 showed that Alendronate is effective in the management of periodontitis
associated bone loss. Gel based local delivery of the drug addresses the critical concern of
exposing the patient to adverse effects of systemic administration.
Bisphosphanates - Alendronate (ALN),

84. the
treatmen
t
of hyperlipidemia
and
Statins– Simvastatin, Atorvastatin, Rosuvastatin
morphogeneti
c
• Lipid lowering drugs– an effective
Approach for arteriosclerosis :
• Statins are specific competitive inhibitors of HMG-
CoA reductase.
• It modulate bone formation by increasing the
expression of bone inflammation, and
angiogenesis.

85. Author Studies Results and conclusion
Pradeep et
al, 2010
Effect of locally delivered SMV gel as LDD in
patients with chronic periodontitis.
– A greater decrease in gingival index
and probing depth and a clinical
attachment level gain with significant
defect fill at sites treated with scaling
and root planing plus locally delivered
SMV gel
to investigate the effectiveness of 1.2%
ATV(Atorvastatin) as an adjunct to scaling
and root planing (SRP) in the treatment of
intrabony defects.
Reduction in PD, CAL gain and
greater mean percentage of
radiographic bonefill … ATV as an
adjunct to SRP can provide a new
direction in the management of IBDs.
Studies

86. Author Studies Results and conclusion
(AR
Pradeep,
2015)
clinical effectiveness of subgingivally
delivered 1.2% rosuvastatin (RSV) gel
incorporated into a methylcellulose vehicle
for its controlled release into intrabony defect
(IBD) sites as an adjunct to scaling and root
planing (SRP) for treatment of patients with
CP
Rosuvastatin in situ gel (1.2%) as
LDD-- greater reduction than placebo
in PD and gingival index, along with
increased gain in CAL
AR
Pradeep,
2016)
To evaluate and compare the efficacy of 1.2%
RSV and 1.2% ATV gel local drug delivery
(LDD), in addition to scaling and root
planing (SRP), for the treatment of intrabony
defects (IBDs) in patients with chronic
periodontitis (CP
LDD of 1.2% RSV results in
significantly greater clinico-
radiographic improvement than 1.2%
ATV or placebo gels as adjunct to
mechanical periodontal therapy.
STUDIE
S

87. Metformin
Effectiveness of MF 1% in an indigenously prepared, biodegradable, controlled-release gel, as an adjunct to scaling and root
planing (SRP) in treatment of vertical defects in smokers with generalized chronic periodontitis (CP) was
investigated….greater decrease in mSBI and PD and more CAL gain with significant IBD fill at vertical defect sites treated
with SRP plus locally delivered MF, versus SRP plus placebo, in smokers with generalized CP
-(Rao. NS et al, 2013)
Satranidazole
Study.. effectiveness of subgingivally delivered satranidazole (SZ) gel as an adjunct to scaling and root planing (SRP) in the
treatment of chronic periodontitis.
Results….greater mean reduction of PD, mean CAL gain and number of sites harboring periodontopathogens…. The use of 3% SZ
gel, when used as an adjunct to nonsurgical periodontal therapy in subjects with periodontitis, achieved better results than initial
periodontal treatment alone. (N Priyanka, 2015)

88. Clarithromycin Gel
Clarithromycin has been used in periodontal treatment as an adjunct to SRP in gel form as
LDD.
Study-- investigate the adjunctive effects of subgingivally delivered 0.5% clarithromycin
(CLM) as an adjunct to scaling and root planing for treating chronic periodontitis in
smokers. Adjunctive use of 0.5% clarithromycin as a controlled drug delivery system
…enhanced the clinical outcome in smokers - (Agarwal E etal, 2012)
Ipriflavone
Ipriflavone (7-isopropoxy iso-flavone) is a synthetic isoflavone derivative that acts
primarily to suppress bone resorption.
Perugini et al - 2003 designed a film dosage form for sustained delivery of ipriflavone into
the periodontal pocket and can also stimulate osteoblasts to form new bone.

89. Taurolidine
A synthetic broad-spectrum antibiotic with antibacterial, anticoagulant and potential
antiangiogenic activities.
Taurolidine, derived from the amino acid taurine, binds to and neutralizes bacterial exotoxins
and endotoxins, or lipopolysaccharides (LPS).
Taurolidine is a novel introduction and might be an alternative in periodontitis treatment.
Zollinger et al – 2015 evaluated in vitro effect via coating the surface with 10 mg/ml
taurolidine and found that this concentration prevented completely biofilm formation of P.
gingivalis. Thus, it can be used as an adjunct to mechanical removal of biofilms

90. Probiotics
• Probiotics are live microorganisms, which when administered in adequate amounts confer a
health benefit on the host by passively occupying a niche that may otherwise be colonized by
pathogens . This tends to limit a pathogen’s ability to bind to tissue surfaces and to produce
virulence factors - (Nadkerny et al., 2014)
• Penela et al - 2016 evaluated the efficacy of the local use of probiotics as an adjunct to
scaling and root planing (SRP) in the treatment of patients with chronic periodontitis offers
clinical benefit in terms of pocket depth reduction in moderate pockets and reduced oral
malodor parameters.
• Mani et al – 2017 evaluated the effects of probiotics in form of lozenges proved to be an
useful adjunct to scaling and root planing in chronic periodontitis patients.

91. Omega 3 fatty acids
• omega-3 polyunsaturated fatty acids (ω-3 PUFAs), including docosahexaenoic acid (DHA) and
eicosapentaenoic acid (EPA), were shown to have therapeutic value and anti-inflammatory and
protective effects in rheumatoid arthritis, cystic fibrosis, ulcerative colitis, asthma, atherosclerosis,
cancer, cardiovascular disease, and periodontitis.
• Hastert et al -2006 revealed that topical application of bioactive products derived from n-3 fatty acids
(including DHA and EPA) confer dramatic protection against inflammation-induced tissue and bone
loss associated with periodontitis in experimental models
• Deore et al -2014 used Omega 3 fatty can successfully reduce gingival inflammation, pocket depth, and
attachment level gain. Dietary supplementation with ω-3 FAs may have potential benefits as a host
modulatory agent in the prevention and/or adjunctive management of chronic periodontitis.

92. Ozonated Olive Oil
• Ozone therapy can be defined as a versatile bio-oxidative therapy in which oxygen/ozone is
administered via gas or dissolved in water or oil base to obtain therapeutic benefits in a
diseased living system.
• Patel PV et al., (2012) evaluated the efficacy of ozonated olive oil(OOO) as a monotherapy
and an adjunct to scaling and root planing in the treatment of chronic periodontitis. The OOO
both as an adjunctive therapy and mono-therapy was efficient in improving periodontal
conditions.
• Shoukheba MYM et al., (2014) evaluated the effect of subgingival application of ozonated
olive oil gel concluded that it could be a promising adjunct to SRP in the treatment of
aggressive periodontitis.

93. Co – Enzyme Q10
• Periodontal pathogens can induce free radicals over-formation and thus may cause collagen
and periodontal destruction.
• Anti-oxidants are used as supplements to counteract the over production of free radicals in
periodontal disease, that can reduce of collagen destruction.
• Coenzyme Q10 serves as an endogenous antioxidant, regenerates other antioxidants,
stimulates cell growth, and inhibits cell death.
• Because it is an antioxidant, coenzyme Q10 has received much research attention associated
with periodontal diseases.
• Perio Q gel may possibly be effective as a topical agent and as an adjunct to scaling& root
planing in treatment of gingivitis and chronic periodontitis.
• Salih et al- 2016 showed that the clinical parameters significantly improved in the phase of
periodontal treatment, indicating that CoQ10 opens new treatment options by improving the
host response to disease activity

94. NSAID’S
• 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.
• Deshpande et al – 2013 evaluated the additional use of local drug delivery of flurbiprofen through gel
media enhances the positive effects of scaling and root planing and helps in faster resolution of the
inflammation.
• Srinivas et al -2011 indicate that the combined effect of locally delivered ketoprofen with SRP was more
effective in controlling periodontal disease than SRP alone.
• Yang et ak – 2007 - Ketorolac tromethamine gel (KT gel) and ketorolac tromethamine gel containing
genipin (KTG gel) were prepared and their therapeutic effects on periodontitis were evaluated. The
KTG gel appears to be effective against gingivitis in the periodontal pocket through its increased anti-
inflammatory activity and cross linking with biological tissues.

95. Local Delivery Of GrowthFactors
• Fibroblast growth factor was found to be a very efficacious introduction in local drug
delivery.
• To regenerate periodontal tissues, a sandwich membrane composed of a collagen sponge
scaffold and gelatin microspheres containing basic fibroblast growthfactor (bFGF) in a
controlled-release system was developed.(Nakahara T et al.2003)
• (Murakami et al., - 1999) demonstrated that bFGF can be applied as one of the therapeutic
modalities which actively induce periodontal tissue regeneration.
• The results of in vitro studies suggest that by suppressing the cyto differentiation of
periodontal ligament cells (PDL) cells into mineralized tissue forming cells, bFGF may play
important roles in wound healing by promoting angiogenesis and inducing the growth of
immature PDL cells, and may in turn accelerate periodontal regeneration.

96. - The severe forms of the disease may be characterized by a decrease in the presence of a
subset of cells responsible for directing immune regulation, Regulatory T cells (Tregs).
- To address the underlying immune dysfunction, we have developed acellular approaches,
utilizing translatable bioerodible microspheres composed of poly(lactide-co-glycolide) capable
releasing factors that can recruit endogenous Tregs and induce local Tregs in the periodontium
for the treatment of periodontal disease.
- Finally, we describe an alternative strategy to bolster Treg population in situ, through the
local expansion of Tregs by PLGA microspheres releasing a combination of transforming
growth factor beta (TGF-β), rapamycin (Rapa) and interleukin 2 (IL-2).
- Administration of TGF-β, Rapa, IL-2 microspheres in a mouse model for periodontal disease
significantly reduced the primary outcome of periodontal disease, alveolar bone resorption.
- Andrew et al - 2016

97. Herbal Products For Periodontitis
Eucalyptus Extract , Neem Leaf , Blood root, Chamomile, Liquorice,
Pomegranate, Propolis, Garlic, Turmeric, Tulsi, Aloevera, Clove, Mango,
Onion, Craneberry , Green tea, Triphala, Miswak, Curcumin and so on.

98. Eucalyptus extract
• Ethanol extracts (60% ethanol) from Euclyptus globulus leaves reportedly posses
antibacterial activity against various bacteria, including oral bacteria.
• It isplayed antibacterial activity against several periodontopathic bacteria, (Porphyromonas gingivalis
and Prevotella intermedia).
• The growth of P. gingivalis was strongly inhibited even with a low concentration (10 mg/ml) of
eucalyptus extracts.
• A double masked study revealed that subjects who chewed eucalyptus containing gum found relief from
the disease's symptoms-- lesser gingival bleeding, reduction in pocket depth and reduced plaque
accumulation. Using toothpaste or tinctures containing eucalyptus extract could benefit the
periodontal condition. (Nagata H.,2008)

99. Neem
• Neem leaf extract can help reduce bacteria and plaque levels that cause the progression of periodontitis.
• Bioactive materials found in neem leads to the presence of gallotannins during the early stages of plaque
formation that could effectively reduce the number of bacteria available for binding to the tooth surface by
increasing their physical removal from the oral cavity through aggregate formation.
• Potential anti-plaque activity -- reduced bacterial adhesion to saliva coated hydroxyapetite.
• A study was done to evaluate the effectiveness of neem (Azadirachta indica) leaf extract against plaque
formation in males between the age group of 20–30 years over a period of 6 weeks. The results of the study
suggested that the gel containing neem extract has significantly reduced the plaque index and bacterial count
than that of the control group (Wolinky LE et al- 2013)

100. Blood root
• Sanguinaria canadensis (bloodroot) -- herbaceous flowering plant native
to eastern North
America.
• The FDA has approved the inclusion of sanguinarine in toothpastes as
an antibacterial or anti-plaque agent.
• Due to its natural alkaloids, bloodroot can curb the growth of
bacteria responsible for periodontal disease.
• reduce inflammation and prevent deepening of periodontal pockets,
thereby preventing bone loss & tooth loss.(Reddy PD, 2010)

101. Chamomile - (Matricaria Recutita)
• an age-old medicinal herb known in ancient Egypt, Greece and which
are a member of the Asteraceae family.
• With its anti-inflammatory and antibacterial properties, chamomile helps
in reducing the inflammation in periodontal tissues and reduces the
bacterial load in the oral cavity. (Reddy PD, Chopra RN et al - 2003)

102. Liquorice
• Liquorice (Glycyrrhiza glabra),-- sweet wood (native to the Mediterranean and certain areas of
Asia).
• A perennial herb with sweet taste; widespread pharmacological effects.
• The most common medical use of liquorice is for treating upper respiratory infections including
coughs, hoarseness, sore throat and bronchitis. (Söderling E, Sasakia H - 2003)
• Antioxidant and hepatoprotective properties inhibit the generation of reactive oxygen species
(ROS) by neutrophils at the site of inflammation. (Racková L- 2006)
• The ability of liquorice to reduce formation of dental plaque contributes to its role
in periodontitis management.

103. Propolis
• Generic name for a complex resinous mixture collected by honey bee from the buds and exudates of various plants.
• It is used for the treatment of aphthous ulcer, Candidiasis, gingivitis, periodontitis, and pulpitis due to its
antimicrobial and anti- inflammatory activities.
• Studies have evaluated the antibacterial action of propolis against certain anaerobic oral pathogens and found it
to be very effective against Peptostreptococcus anaerobius, Lactobacillus acidophilus, Actinomyces naeslundii,
Prevotella sp., Porphyromonas gingivalis, Fusobacterium nucleatum and Veillonella parvula. (Gebara EC - 2012)
• A study was aimed at the clinical and microbiological evaluation of the efficacy of subgingivally delivered Indian
propolis extract as an adjunct to scaling and root planing (SRP) in the treatment of periodontitis. Subgingival
delivery of propolis showed promising results as an adjunct to SRP in patients with chronic periodontitis when
assessed by clinical and microbiological parameters.

104. Aloe Vera
• The medicinal value of the plant lies in a gel-like pulp obtained on peeling the leaves.
• These substances include …. Lignins, Saponins, Vitamins, aminoacids, anthraquinones etc.. improves wound
healing by Increasing blood supply, which increased oxygenation as a result.
• potent free radical and superoxide anion scavenging properties. (Yagi et al. in 2002 )
 STUDIES:
• Aim : To evaluate the effect of aloe vera gel as an adjunct to scaling and root planing (SRP) in the management
of chronic periodontitis.
• SRP-ALOE group showed significantly better results than SRP alone. (Harjit Kaur ,2012)
• Geeta Bhat et al, 2011 in her study concluded that its use in local drug delivery results in significant reduction
in pocket depth and resulted in reduction in the gingival index.

105. Turmeric
• It has proven properties like Anti-inflammatory, antioxidant, antimicrobial,
hepatoprotective, antiseptic, accelerates wound healing.
• study… evaluate the adjunctive efficacy of turmeric, curcumin, and traditional
nonsurgical methods for treating periodontal pockets.
• Plaque index and gingival index scores showed significant improvement from
baseline through the end of the study. (Kudva P et al,2012)
• The experimental local drug-delivery system containing 2% whole turmeric gel can be
effectively used as an adjunct to scaling and root planing and is more effective than
scaling and root planing alone in the treatment of periodontal pockets. (Roobal Behal
et al. 2011)

106. Pomegranate – Punica gratum
• A clinical study conducted by Sastracaha et al (2003) concluded that
extracts of Punica granatum plus scaling and root planning
significantly reduced the clinical signs of chronic periodontitis.
• Vasconcelos et al (2006) investigated the antimicrobial effect of
Punica granatum Linn (pomegranate) phytotherapeutic gel and
concluded that Punica granatum L. gel had greater efficiency in
inhibiting microbial adherence in oral cavity.

108. Herbal Combinations
• Along with individual herbs, herbal combinations can combat periodontitis.
• Mixture of peppermint oil, menthol, chamomile, clove oil.. can reduce periodontitis
symptoms.
World Journal of Pharmaceutical Research Vol 3, Issue 2, 2014.

109. Novel Chitosan-pva-based Local Delivery
• Chitosan is a natural polysaccharide.
• physically or chemically crosslinked to prepare microspheres, films and gels.
• These stable chitosan-based depot systems have been investigated for treatment of various diseases
including cancer and bacterial infection.
• Localized drug delivery system with chitosan and poly vinyl alcohol (PVA) for treating severe periodontitis
has been designed that delivered antibacterial agent ornidazole into gingival crevicular fluid. (Wang LC
etal) …

110. Local Drug Delivery’s Impact on Deep Probing Depths ( > 7 mm)
110
• As probing depths increase, SRP becomes less efficient; therefore investigators evaluated the potential benefit
of employing local drug delivery at deep sites (>7 mm).
• Timmerman et al.(1996) reported that there was no benefit of employing 2% minocycline gel as an adjunct to
SRP to reduce probing depths at deep sites, whereas Van Steenberghe et al.(1999) noted that combined therapy
provided a better result than SRP alone at sites >7 mm deep.
• In summary, sites with deep probing depths provide an opportunity to attain greater probing depth reductions
than shallow pockets.
• However, there are limited data related to the ability of individual drug delivery systems to enhance probing
depth reductions at pockets >7mm.
• Therefore, this facet of therapy requires further study.

111. Inhibition of Periodontal Disease Progression
11
1
Garrett et al 1999 compared doxycycline gel versus SRP and found that there was no
statistically significant benefit regarding inhibition of disease progression associated with drug
therapy.
Jeffcoat et al 2000, after employing chlorhexidine chips plus SRP, noted that these sites
achieved a mean 0.1 mm gain of bone, whereas 15% of the sites administered SRP alone lost bone
(0.04mm) during a 9-month clinical trial.
Overall, it is difficult to project outcomes regarding the ability of local drug delivery to inhibit
disease progression because a limited number of studies, diverse study
protocols, and different thresholds for disease progression were used.

112. Impact of Local Drug Delivery on Furcations
Tonetti et al.(1998) reported that tetracycline fibers in conjunction with SRP initially provided
a Better result than SRP alone at molar furcations; however, after 6 months, there were no
statistically significant differences with respect to mean probing depth reduction or gain of
clinical attachment.
In contrast, Williams et al. and Meimberg et al.(2002) noted a statistically significant greater
probing depth reduction in molar furcation when SRP plus minocycline microspheres were
compared to SRP alone.
Additional studies are needed to assess the effect of local delivery in a variety of defects to include
furcations and intrabony lesions.

113. Repair of Osseous Defects
Bone deposition in infrabony defects is a desirable treatment outcome; however, the amount of
bone fill that occurred after local drug delivery is limited.
Aimetti et al.(2004) reported that tetracycline fibers plus SRP resulted in 0.94 mm bone deposition
in osseous defects versus 0.09 mm after SRP alone.
In general, results regarding bone fill need to be interpreted in light of the fact that other clinical
procedures provide better bone repair in osseous defects.

114. The strategic approaches with associated challenges and achievements towards the formation
of periodontal drug delivery system :
114
Strategy 1: systemic delivery devices
Low benefit to risk ratio, ingestion of large drug doses
Inadequate drug concentration at periodontal site
Rapid/non-sustained drug release
Poor patient compliance: frequent administration
No penetration of delivery system
No adhesion/retention into periodontal pocket High incidence of bacterial resistance

115. Strategy 2: local mouth rinses and dental irrigation
115
Inadequate drug concentration at periodontal site
Drug dose is reduced
Rapid/non-sustained drug release
Systemic toxicity is decreased
Poor patient compliance: frequent administration
No penetration of delivery system
No adhesion/retention into periodontal pocket
High incidence of bacterial resistance

116. Strategy 3: non-biodegradable, intrapocket fibres, strips, films and microparticles
116
Poor patient compliance: discomfort during the placement of device, at least two visits to
therapist is required and development of foreign body response, if left in situ
Adequate drug concentration at periodontal site Poor penetration of system or drug.
Prolonged/sustain drug release
Poor retention of system into periodontal pocket
Less frequent administration
Low incidence of bacterial resistance

117. Strategy 4: biodegradable, intra-pocket fibres, strips, films and
microparticles
117
Poor patient compliance: discomfort during placement
Visit to therapist is reduced
Poor penetration of system/drug
No foreign body response
Poor retention of system into periodontal pocket
Low incidence of bacterial resistance

118. Strategy 5: biodegradable nanoparticles
118
Poor retention of system into periodontal pocket
Placement is easier
Low incidence of bacterial resistance
Good penetration due to nano-sized particles
Strategy 6: Mucoadhesive, biodegradable nanoparticles
Low incidence of bacterial resistance
Good retention of system
Strategy 7: antibiotic-free, mucoadhesive, biodegradable
nanoparticles
Bacterial resistance does not develop

119. • There is ample evidence to show that locally delivered antimicrobials can reduce clinical and
microbial parameters to a level, if not better than, at least comparable to that of scaling and
root planing.
• Mechanical instrumentation, can be technically demanding, time consuming, and in
some periodontal defects, ineffective or incomplete.
• LDD on the other hand is simple to use and may conceivably in the future be delivered by the
patient themselves, hence can be used as an adjunct to mechanical plaque removal.
Conclusion

120. References
120
• Carranza’s Clinical Periodontology - 10th Ed.
• Tetbook of Periobasics – Nitin Saroach
• Pramod Vishwanath Prasad et al. Bird’s Eye View on the Recent Advances in Drug Delivery
Systems. Journal of Biomaterials and Nanobiotechnology, 2011, 2, 544-556
• Vidya Dodwad et al. Magic Bullet to treat Periodontitis: A targeted approach. JPBMS, 2012,
20 (19)
• Amit Bhardwaj et al. Advances in periodontal drug delivery systems. International Journal of
Novel Drug Delivery Technology. Jan-Mar 2012, Vol-2, Issue-1
• Vidya Dodwad et al. Local Drug Delivery In Periodontics: A Strategic Intervention.
International Journal of Pharmacy and Pharmaceutical Sciences. Vol 4, Issue 4, 2012

121. • K. Schwach-Abdellaouia, N. Vivien-Castionib, R. Gurny. Local delivery of antimicrobial agents for the
treatment of periodontal diseases. European Journal of Pharmaceutics and Biopharmaceutics 50
(2000) 83-99.
• Mahesh R. Dabhi et.al. Formulation development of smart gel periodontal drug delivery system for
local delivery of chemotherapeutic agents with application of experimental design. Drug Delivery,
2010; 17(7): 520–531.
• Arthur J. Bonito et al. Impact of local adjuncts to scaling and root planing in periodontal disease
therapy: A systematic review. J Periodontol 2005;76:1227-1236.
• R.J, Oringer et.al.effect of locally delivered Minocyclin microsphere on marker of bone resorption. J
Periodontol 2002;73:835-842.

122. • Maria Pavia,Carmelo G.A. Nobile, and Italo F. Angelillo. Meta- analysis of local tetracycllin in
treating chronic periodontitis. J Periodontol 2003;74:916-932.
• Maria Emanuel Ryan. Nonsurgical Approaches for the Treatment of Periodontal Diseases. Dent Clin N
Am 49 (2005) 611–636
• Pragati S, Ashok S., Kuldeep S. Recent advances in periodontal drug delivery systems . International
Journal of Drug Delivery 1(2009) 1-14
• Gary Greenstein. Local drug delivery in the treatment of periodontal disease: assessing the clinical
significance of the results. . J Periodontol 2006;77:565-578.
• Killoy WJ: The clinical significance of local chemotherapies. J Clin Periodontol 2002; 29 (Suppl 2):
22–29

123. Thank you