local drug delivery in periodontology

1. SAHLA AMBADI
PG- II
LOCALDRUG
DELIVERY

2. CONTENT
• INTRODUCTION
• HISTORY
• CLASSIFICATION
• INDICATION &CONTRAINDICATIONS
• ADVANTAGES AND DISADVANTAGES
• LOCAL DRUG DELIVERY DEVICES
• LOCAL DRUG DELIVERY AGENTS
 Tetracycline
 Doxycycline
 Minocycline
 Chlorhexidine
 Metronidazole
• NEWER AGENTS IN LDD
• CONCLUSION
• REFERENCE

3. INTRODUCTION
Periodontal diseases…. plaque biofilm.
Periodontal destruction….. result of…
Removal of biofilm by ……

4. To overcome this, Antimicrobials both systemic and locally acting were used as adjuncts to
mechanical therapy
• unfavorable anatomy of the tooth
•presence of tissue invasive organisms
• bacterial invasion into dentinal tubules
Quirynen et al (2002)
Limitations of mechanical debridement

5. drug toxicity
drug interaction
acquired bacterial resistance
Patient compliance
• 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 ..

6. Local delivery of antibacterial agents into periodontal pocket
limiting the drug to its target
site
Achieve high concentration at
target site
Dr. Max Goodson (1979) …. developed local delivery of therapeutic agents into a viable concept.

7. Local route of drug delivery can attain 100-fold higher
concentrations of an antimicrobial agent in subgingival sites
compared with a systemic drug regimen thereby reducing
the total patient dose by over 400 fold avoiding development
of drug-resistant at non oral body sites.
(Goodson J., 1994).

8. HISTORY
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…

10. CLASSIFICATION OF LOCAL ANTIMICROBIAL THERAPY IN PERIODONTICS
• based on their mechanism of action (Langer & Peppas (1988) --
Diffusion controlled systems
Chemically controlled systems
Solvent activated System
Release induced by external forces

11. Matrix (monolithic) Reserviour (membrane devices)
Diffusion controlled system

12. Chemically controlled system

13. Solvent activated
System
- Osmotic system
- Swelling controlled
system
Release induced by
external forces
Magnetically controlled
systems

14. Reservoir without rate
controlling system:
• hollow fibers filled with a
therapeutic agent in which the
agent is released simply by
diffusion through the reservoir
wall.
Reservoir devices with rate
controlling system:
• solvent action on coated drug
particles, microporous polymer
membrane or erodable polymeric
matrices.
-- based on the rate controlling system-- Kornman

15. PERSONALLY APPLIED
(In patient home self-care)
PROFESSIONALLY APPLIED
(In dental office)
NON-SUSTAINED SUBGINGIVAL DRUG
DELIVERY
SUSTAINED SUBGINGIVAL DRUG
DELIVERY
depending on the type of therapy.. Rams & slots(1996)

16. A) SUSTAINED
RELEASE DEVICES
Drug delivery for less than 24 hrs
require multiple applications
) CONTROLLED
DELIVERY DEVICES
Duration of drug release exceeds 24hrs
administered once
Based on duration of action (Greenstein & Tonetti 2000)

17. INDICATIONS
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
who are
suffering from
recurrent
periodontitis.
During
periodontal
regenerative
procedures.

18. CONTRA-INDICATIONS
with known
hypersensitivity
reaction to
antimicrobials
Those requiring
multiple areas
of treatment.
As replacement
or SRP,
replacement for
surgical
therapy.
asthmatics,
infective
conditions (AIDS,
TB)

19. ADVANTAGES:
• limit drug at the target site.
• No risk of emergence of resistant
microorganism.
• Minimizing the exposure of total body to
the drug.
• Sustained release of antimicrobial in the
periodontal pockets.
DISADVANTAGES
•Difficulty in placing into deeper parts of
pockets and furcation lesions.
•Patient compliance and manual dexterity.
•Time consuming and labour intensive in-
patients with numerous advanced lesions.
•Do not markedly affect pathogens residing on
extra-pocket oral surfaces.
•Non-sustained drug delivery provides only a
brief exposure of the target microorganism to the
applied antimicrobial agent.

20. IDEAL REQUIREMENTS FOR LOCALANTIMICROBIAL AGENTS:
• 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. (Goodson 1985)

21. VARIOUS DRUG DELIVERY DEVICES :
FIBERS
• FILMS
• INJECTABLE GELS
• STRIPS AND COMPACTS
• VESICULAR LIPOSOMAL SYSTEMS
• MICROPARTICLE SYSTEM
• NANOPARTICLE SYSTEM

22. 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)

23. Fibers
• 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.

24. 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

25. Both degradable and non- degradable films are available.
Advantages-
• 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.

26. 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.

27. • A higher biocompatibility and bioadhesivity, 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%).

28. 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.

29. • 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.

30. Vesicular Systems
• Designed to mimic the bio-membranes in terms of structure and biobehaviour, and hence are
investigated intensively for targeting periodontal biofilms.

31. • The targeting of liposomes was thought to be because of the interaction of 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.)

32. 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.

33. • PLGA microspheres containing minocycline … have been used for the elimination of
Porphyromonas gingivalis from the periodontal pocket.
• .. 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.

34. 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

35. • 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
polyethyleneglycol dimethacrylate (PEGDMA) could be used as a drug delivery system
for dental applications.

36. • 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.)
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)

37. ) 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.
• Incorporation of the HLE into a colloidal carrier improved its antibacterial performance and
diminution of the bactericidal concentration was observed.

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

39. 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.

40. 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 a
period of 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.

42. • In a 60-day multicenter study - 107 periodontitis patients after supragingival scaling,…
• Four non-adjacent teeth (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 )
• … 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)
.

43. • 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…...
• enables the 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)

44. • 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(Maheshwa ri etal)

45. 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)-3
months
.
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

46. 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.

47. 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.

48. • 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.

49. 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

50. 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

51. 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.

52. 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.

53. 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 a
disposable plastic cartridge affixed to a
stainless-steel handle .

54. 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.

55. 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.

56. author 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.
STUDIES

57. 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.

58. Elyzol
• metronidazole 25% in a mixture of glyceryl mono-oleate and sesame oil.
Contains metronidazole benzoate- active agent.
• 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.

59. author 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-
month)
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

60. 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.

61. • 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.

62. • 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.

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

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

65. • 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.

66. 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.

67. 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

68. 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.

69. NEWER TRENDS IN LOCAL DRUG DELIVERY
• DRUGS FOR OSSEOUS DEFECTS
• Alendronate
• - a novel bisphosphonate; very potent inhibitor of bone resorption.
• 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)

70. • Statins– Simvastatin, Atorvastatin, Rosuvastatin –
• Lipid lowering drugs-- an effective approach for the treatment of hyperlipidemia and
arteriosclerosis.
• Statins are specific competitive inhibitors of HMG-CoA reductase.
• modulate bone formation by increasing the expression of bone morphogenetic protein-2,
inflammation, and angiogenesis.

71. author 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

72. author 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.
STUDIES

73. • 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)

74. 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)

75. 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.).

76. HERBAL PRODUCTS FOR PERIODONTITIS
• Eucalyptus Extract
• Neem Leaf
• Bloodroot
• Chamomile
• Liquorice
• Propolis
• Aloevera

77. • Eucalyptus extract
• Ethanol extracts (60% ethanol) from Euclyptus globulus leaves reportedly possess
antibacterial activity against various bacteria, including oral bacteria.
• displayed 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.

78. • 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.

79. 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.

80. • 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.)

81. Bloodroot
• 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)

82. • 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)

83. 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)

84. • antioxidant and hepatoprotective properties… inhibit the generation of reactive oxygen
species (ROS) by neutrophils at the site of inflammation. (Racková L)
• The ability of liquorice to reduce formation of dental plaque contributes to its role in
periodontitis management.

85. Propolis
• generic name for a complex resinous mixture collected by honey bee from the buds and exudates of various
plants.
• 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)

86. 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. Twenty patients diagnosed with chronic periodontitis presenting a minimum of two pockets (probing depth
≥5 mm) were selected. Sites were assigned randomly into control sites (n=20) which received SRP alone or test sites (n=20)
which received SRP and locally delivered propolis. At selected sites, the clinical parameters were assessed and subgingival
plaque samples were collected at baseline, 15 days and one month. The samples were cultured 76 anerobically for
periodontal pathogens. The results indicated that there was a significant improvement in both clinical and microbiological
parameters (p<0.01) in the test sites compared to the control sites at the end of the study. Subgingival delivery of
propolis showed promising results as an adjunct to SRP in patients with chronic periodontitis when
assessed by clinical and microbiological parameters.

87. • 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 )

88. 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.

89. • 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

90. • 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)

91. • 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.

92. 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.

93. LOCAL DELIVERY OF GROWTH FACTORS
• 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)

94. • 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) …

95. • As a monotherapy, LDDsystems incorporating a variety of drugs can improve periodontal health.
• There is no single universal drug that would be effective in all situations. Therefore, at non-responsive sites,
bacterial and antibiotic sensitivity testing may be necessary to determine putative pathogens and their
susceptibility to specific antimicrobial agents.
• LDD often appears to be as effective as scaling and root planing with regards to reducing signs of periodontal
inflammatory disease.
• Local delivery may be an adjunct to conventionaltherapy. The sites most likely to be responsive to this
adjunctive treatment method may have refractory or recurrent periodontitis, or specific locations where it is
difficult o instrument root surfaces.
SUMMARY

96. CONCLUSION
• 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.

97. REFERENCES
• Clinical Periodontology- Carranza 9th/10 th edition
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2013;4(2):39-49.
• Local antimicrobial therapy - Perio 2000 vol 10,1996:139-159
• Advanced Drug Delivery Systems in Treating Periodontal Diseases-A Review- IOSR Journal
of Dental and Medical Sciences (IOSR-JDMS)

98. • LOCAL DRUG DELIVERY IN PERIODONTICS: A STRATEGIC INTERVENTION International Journal
of Pharmacy and Pharmaceutical Sciences Vol 4, Issue 4, 2012
• Local drug delivery in Periodontics: A tactical entreaty- Journal of Research in Pharmaceutical Science
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99. • Goodson JM. Antimicrobial strategies for treatment of periodontal diseases. Periodontol 2000
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