LOCAL DRUG DELIVERY

DR DEVIKA G
IST YEAR PG
 CONTENTS
INTRODUCTION
SYSTEMIC THERAPY - DRAWBACKS
HISTORY
RATIONALE OF USING LOCAL DRUG DELIVERY
CLASSIFICATION
IDEAL REQUIREMENTS OF AN LDD
INDICATIONS
CONTRAINDICATIONS
ADVANTAGES
DISADVANTAGES
LOCAL DRUG DELIVERY AGENTS
VARIOUS DRUGS USED AS LDD
PHYTOTHERAPEUTIC AGENTS
LOCAL DELIVERY OF ANTIMICROBIAL AGENTS AND PERIIMPLANT MUCOSITIS /
IMPLANTITIS
CONCLUSION
REFERENCE
INTRODUCTION
‘Periodontal disease’’ includes various degenerative and
inflammatory states of gums, periodontal ligaments,
alveolar bone and dental cementum
Jain et al., 2008

Various local or systemic approaches were used for an

effective treatment of periodontitis
Antibacterial agents used along with mechanical
debridement in the management of periodontal infection.

The effectiveness limited due to lack of accessibility in

the pocket

Effective treatment, the antibiotic must reach the depth

of the pocket
 SYSTEMIC THERAPY - DRAWBACKS?

Side effects including hypersensitivity, gastrointestinal

intolerance and the development of bacterial resistance

Poor results because active product could not achieve an

adequate concentration at the site of action

Inability of the active product to be retained locally for a

sufficient period of time.
Mombelli A, etal; 1997
Drawbacks would be markedly reduced if antimicrobial
agents applied locally

Local tissue concentration of a drug can be enhanced by

incorporating the active agent into controlled release delivery
systems to be placed directly in the periodontal pocket

Vandekerckhove BNA et al, 1997

 HISTORY

1979, Dr. Max Goodson et al first

proposed the concept of controlled
delivery in the treatment of periodontitis

Goodson JM, etal ;1979

RATIONALE OF USING LOCAL DRUG
DELIVERY

to place an antibiotic or antiseptic in direct

contact with the root surface, so that pathogenic
microorganisms that are not accessible to
mechanical debridement by hand or power driven
instruments, can be reduced or eliminated

a high concentration (many folds more than the

minimum inhibitory concentration) can be
attained at a site for a sufficient duration of time
 CLASSIFICATION
Basedon
Based onthe
theapplication
application[Rams
[Ramsand
andSlots]
Slots]1996
1996
Personally applied (in patient home self-care)
Personally applied (in patient home self-care)
Non sustained subgingival drug delivery
 Nonoral
Home sustained subgingival drug delivery
irrigation
• Home oral irrigation
Home
• Home oraloral
irrigation
irrigationjetjettips
tips
• Traditional
Traditional jetjet tips
tips
• Oral irrigation (water pick)
Oral irrigation (water pick)
• Soft cone rubber tips (pick pocket)
 Sustained
Soft cone rubber tips (pick
subgingival pocket)
drug delivery
Sustained subgingival drug delivery
Professionally applied (in dental office)
Professionally applied (in dental office)
Non sustained subgingival drug delivery
 Non sustained subgingival drug delivery
Professional pocket irrigation
• Professional pocket irrigation
Sustained subgingival drug delivery
 Sustained subgingival drug delivery
Controlled release devices
• Controlled release devices
Hollow fibres
• Hollow fibres
Dialysis tubing
• Dialysis tubing
Strips
• Strips
Films
• Films
BASED ON THE DURATION OF MEDICAMENT RELEASE
(GREENSTEIN AND TONETTI 2000)

Sustained release Controlled release

devices devices
• Designed to • Designed to
provide drug provide drug
delivery for less release that at
than 24 hours least exceeds 1
day or for at least
3 days following
application
(Kornman1993)
DEPENDING ON DEGRADABILITY

1. Nondegradable devices
(first generation)

2. Degradable devices
(second generation) (Divya
P.V, etal; 2010)
Based on their mechanism of action (Langer & Peppas ;1988)
1.Diffusion controlled systems
-reservoirs
Based on their(membrane devices)
mechanism of action (Langer & Peppas ;1988)
-matrices (monolithic device)
1.Diffusion controlled
2.Chemically controlledsystems
systems
-reservoirs (membrane devices)
-bio-erodible systems
-matrices (monolithic device)
-pendant chain systems
2.Chemically controlled systems
3.Swelling controlled
-bio-erodible systems
systems
-pendant chain
4.Magnetically systems
controlled systems
3.Swelling controlled systems
4.Magnetically controlled systems
IDEAL REQUIREMENTS OF AN LDD

Deliver the drug to the base of the pocket

Deliver the drug at a desired concentration, which is

effective in killing microorganisms

Must sustain the concentration of the drug in the

pocket for a sufficient duration of time.

Should be easily placed and manipulable

Must be retained in place after initial placement.

Should be biodegradable.

Should not give rise to bacterial resistance.

Should be safe to use with minimal side effects.

Should be effective only against periodontal pathogens

and not on commensal microflora
 INDICATIONS
As an adjunct in the treatment of few localized
nonresponding sites in an otherwise controlled patient.

Ailing and failing implant cases where surgical

intervention is not indicated or will yield a compromised
result.

In medically compromised patients where surgical

procedures are not recommended.
Periodontal maintenance therapy.

Patient with gastrointestinal intolerance to systemic drug

medication.
Grade II furcation involvements (shallow or deep) when
surgical interventions is not planned.
CONTRAINDICATIONS
Patients with history of allergy to a particular
antimicrobial agent.
In pregnancy and lactating periods.
Children under the age of 12 years.

Patients with complete renal failure.

Patients susceptible to infective endocarditis.

As a replacement to scaling and root

planning during initial periodontal therapy
As a replacement for surgical periodontal
therapy in cases indicated for periodontal
surgery.
 ADVANTAGES
High concentration
High concentration ofdrug
of the the drug
can becan be achieved
achieved at asite
at a localized localized
site
maintained maintained thereforlong
there long enough enough
the desired fortothe
effect be desired effectwithout
accomplished to
be accomplished
causing without causing any side effects.
any side effects.
Independent of patient compliance.
Independent of patient
Does not harm the symbioticcompliance.
useful microflora of gastrointestinal tract.
Systemic intolerance is bypassed
Does not harm the symbiotic useful microflora of
gastrointestinal tract.

Systemic intolerance is bypassed

Concentration of drug in periodontal pocket is not
affected by the fluctuation in plasma levels.

Technique is suitable for agents which cannot be given

systemically, such as chlorhexidine

Suprainfection and drug resistance are rare.

Reduction in total drug usage as compared to

conventional therapy.

Reduction in frequency of drug administration

 DISADVANTAGES
Difficulty in Complete drug
placing of penetration is
therapeutic not possible and
concentrations of extra pocket
the antimicrobial sites are
agents in deeper unaffected.
sites.

Has to be
professionally
placed or if
manually
placed, requires
manual
dexterity and
patient
compliance.
 LOCAL DRUG DELIVERY AGENTS
Fibres

Microparticles
Films
,nanoparticles

Injectable
Compacts systems

Strips Gels
 FIBERS
Thread like devices
Placed circumferentially into the pockets with an
applicator
Secured with cyanoacrylate adhesive for the
sustained release of the trapped drug into the
periodontal pockets

Jain et al., 2008

2017
Tetracycline as local drug delivery in treatment of chronic
periodontitis: A systematic review and meta-analysis

Monali Amit Shah etal 2017

Authors Medicament Conclusion

Sneha Kataria etal Tetracycline Tetracycline fiber therapy along

(2018) with scaling and root planing
improves periodontal parameters
and significantly reduces
bacterial colony count in
treatment of chronic periodontitis
Sachin Sinha etal Tetracycline Tetracycline fiber therapy along
(2014) with scaling and root planing
improves the healing outcome
Johnston et al. Ciprofloxacin, Sufficient release of drug from
(2013) Diclofenac the fibers inhibited growth of E.
sodium coli, E. faecalis and S. mutans
over 10 days
Authors Medicament Conclusion
Sachdeva & Agarwal Tetracycline Refinement of
(2011) periodontal parameters
for duration of 3 months

Chang et al. (2008) Gentamicin sulfate Growth of

Stapyhlococcus
epidermidis was
suppressed up to
2 weeks

Ahuja et al. (2006) Amoxicillin Drug levels remained

trihydrate above MIC for 11 days,
and controlled
delivery was obtained
 DISADVANTAGES
Discomfort during the system placement and gingival redness
(Vandekerckhove et al., 1997)
Dislodging of the fibers during treatment (Anderson, 1996)
Need for removal on a weekly basis proved troublesome for both the
patient and the clinician (Goodson et al., 1991)
 GELS
posses a higher biocompatibility and bioadhesivity

allowing adhesion to the dental pocket

rapidly eliminated through normal catabolic pathways

decreasing the risk of anaphylactic reactions at the

application site

Garg et al, 2014

2017
Author Medicament Conclusion
Dharmendra 0.75% boric acid boric acid gel
Kanoriya etal 2018 delivered
subgingivally to
non‐surgical
periodontal
treatment seems to
be a safe and
effective application
in the treatment of
patients with CP
Sandeep Singhal 0.75% boric acid .75% BA group
etal 2018 showed significant
improvement in
clinical parameters
compared to placebo
gel as an adjunct to
Authors Medicament Conclusion

Avani R. Pradeep 1% alendronate Local delivery of 1%

etal 2017 1.2% atorvastatin ALN results in
significantly greater
improvement in PD,
CAL, IBD depth, and
DDR% as compared
to 1.2% ATV gel.
A.R. Pradeep etal 1.2% Rosuvastatin LDD of 1.2% RSV
2016 1.2% Atorvastatin results in
significantly greater
clinico‐radiographic
improvement than
1.2% ATV or placebo
gels as adjunct to
mechanical
periodontal therapy.
 FILMS
matrix delivery systems

Commonly used for intrapocket delivery

Drugs are released by diffusion and/or matrix dissolution or

erosion

Methods of preparation include solvent casting and direct milling

Garg & Goyal, 2014

 MERITS

easy insertion
appropriate sizing
less discomfort to the patient

Pragati et al., 2011

Adequate adhesiveness and having thickness less than 400 mm not

easily dislodged by daily oral hygiene practice
Author Medicament Conclusion
Abeer Ahamed metformin local application of the
Kasim etal 2017 hydrochloride mucoadhesive
multiple layer films
loaded with metformin
hydrochloride was
able to manage
moderate chronic
periodontitis.
Gayasuddin Khan Metronidazole local delivery of both
etal 2016 Levofloxacin drugs in a sustained
release formula
enhances the
therapeutic effect of
SRP as demonstrated
by the measured
clinical parameters
Author Medicament Conclusion
Labib et al. (2014) Metronidazole Clinical use proved
to be advantageous;
a burst release was
observed during first
2 hours

Shifrovitch et al. Metronidazole Considerable fall in

(2009) bacterial viability,
good biocompatibility
and inhibition of
Bacteroides fragilis
growth
 STRIPS
Thin and elongated matrix band made up of flexible polymer
Position securing mechanism
Accommodating a wide range of interproximal spacing and
having drugs dispersed throughout the polymer

Schwach-Abdellaoui et al., 2000

Solvent casting method and pressure melt method have been
used for fabrication of strips (Pragati et al., 2011)
Once a strip is placed in periodontal cavity, the
polymer swells, expands, and reaches narrow
crevices and furcations of the treated cavity,
carrying active agent throughout the cavity
DISADVANTAGE

Nonbioabsorba
ble

Impair the removed

regenerating after
tissue therapy
Risk of leaving injurious acrylic material in the
periodontal pocket during the removal of the strip

Disadvantages avoided by the use of bioabsorbable

materials
MICROPARTICULATE
SYSTEM
biodegradable as well as non-biodegradable polymeric
materials

Solid spherical polymeric structures (1–1000 mm) … drug

dispersed throughout the polymeric matrix

Jain et al, 2008; Jayaprakash et al., 2009

Free-flowing powders and provide sustained and
controlled drug release at target site

They can be used to form chip, dental paste or can be

directly injected into the pocket
 shielding of unstable drug before and after
administration

controlled drug release

MERITS
improved patient compliance

sustained therapeutic effect

enhanced bioavailability

decreased frequency and intensity of adverse effects

Garg et al., 2013

Authors Medicament Conclusion
Silvana Gjoseva etal doxycycline Chitosan & ethyl
2018 cellulose coated
microparticles
potentiate the anti-
inflammatory effect
of doxycycline.

ThawatchaiPhaecha Doxycycline hyclate Doxycycline hyclate

mud etal 2016 loaded bleached
shellac
microparticle
was a suitable
formulation for
periodontitis
treatment
 PERIODONTAL CHIP
 pharmaceutical composition
 provided in the form of the gel, sheet, film or bar like
formulation
 Periocol-CG small, orange brown in a rectangular
chip form ,rounded at one end for easy insertion into the
periodontal pockets
Author Medicament Conclusion

Malvika Singh etal chlorhexidine chip Local drug delivery using

2018 chlorhexidine chip enhances the
benefit of SRP in the treatment of
chronic periodontitis

Kranti Konugant etal Flurbiprofen and The combination of SRP and

2016 Chlorhexidine Chip subgingival delivery of flurbiprofen
or chlorhexidine chip was more
effective than SRP alone in
improving the clinical parameters
 NANOPARTICLES
submicroscopic solid material with size ranging from 1-
100nm
The drug is dissolved, entrapped, encapsulated, or attached
to a nanoparticle matrix
• Highly dispersible in aqueous medium
• controlled release rate
• enhanced stability
• can access sites unreachable
• uniform drug distribution

Garg et al., 2013

VARIOUS NANOPARTICLES

Nanopores, Nanotubes,
Fullerenes, Quatumdots,
Nanoshells, Dendrimers,
Liposomes, Nanospheres,
Nanorods, Nanowires,
Nanocapsules , Nanowires
NANOPORES
diameters less than 20nm
play vital roles in biosensing and drug delivery

Duan R, etal; 2013

QUANTUM DOTS
Non -toxic indium phosphide quantum dots

synthesized by solvo thermal method

embedded into the dental resin

to tune the emission color of the resin.

 periodontal therapy it
improves the healing
of the periodontal
inflammation provided
by the cadmium-free
and lead-free quantum
dots
LIPOSOMAL DRUG
DELIVERY Mimic the bio-membranes in
terms of structure and bio-
behavior (Jain et al., 2008)

• Microscopic lipid based vesicles

• may be unilamellar or multilamellar

• manufactured by using cholesterol, nontoxic

surfactants, sphingolipids, glycolipids, long-chain fatty
acids, and even membrane proteins
Multilamellar vesicle: 0.1–5.0 mm
Small unilamellar vesicle: 0.02–0.05 mm
Large unilamellar vesicle : 0.06 mm and greater

Garg & Goyal, 2014

ADVANTAGES

Biocompatible
Guard the
encapsulated
drug from Biodegradable
external
environment

High
Nontoxic
stability

Nonimmunogenic
Garg et al., 2013
DISADVANTAGES
High
production
cost

Short
half-life

Leakage of
encapsulated
drug/molecules
Author Medicament Conclusion
FangHu etal 2018 Doxycycline Liposomal-
Doxycycline
Nanoparticles have
good potential for
use in the
treatment of
periodontal and
other
inflammatory
diseases
GENE DELIVERY USING BUBBLE LIPOSOMES
FOR PERIODONTAL THERAPY

Combination of Bubble liposomes and

ultrasound provides an efficient
technique for delivering plasmid DNA
into the gingiva

Technique can be applied for the delivery

of a variety of therapeutic molecules into
target tissue, and may serve as a useful
treatment strategy for periodontitis.
COMMONLY USED LDD
VARIOUS DRUGS USED AS LDD

TETRACYCLINE

• 1st local delivery product available in the US

• Tetracyclines are a group of closely related
bacteriostatic antimicrobials
• frequently used in treating refractory periodontitis,
including localized aggressive periodontitis.
TETRACYCLINE FIBRES
Ethylene/ vinyl
acetate copolymer
Non- fiber (diameter, 0.5
resorbable mm) containing
biologically tetracycline, 12.7 mg
inert, per 9 inches

Generally
considered
safe,
plastic
copolymer
ACTISITE tetracycline fibres ethylene and vinyl-
acetate loaded with 25% w/w tetracycline HCI powder
packaged as a thread of 0.5 mm in diameter and 23 cm
in length. Maintains constant conc of active drug in the
GCF in excess of 1000 μg/mL for a period of 10 days

PERIODONTAL PLUS AB base of collagen film; offers

the advantage of no second appointment for removal as
it biodegrades within 7 days
GEL

 Tetracycline-Serratiopeptidase-Containing
PERIODONTAL GEL

 Bioerodible Injectable Poly (ortho ester) for

Tetracycline Controlled Delivery formulations
tetracycline 10% or 20%
 Prasad Shyamrajan Nadig etal 2019

Tetracycline as local drug delivery in treatment of chronic

periodontitis: A systematic review and meta-analysis

Significant improvement in periodontal parameters such

as CAL, PD, and sulcular bleeding index in favor of
tetracycline as local drug delivery compared to placebo.
 Sneha Kataria etal 2018

Effect of tetracycline HCL

(periodontal plus AB)
on Aggregatibacter
actinomycetemcomitanslevels in
chronic periodontitis

When compared with scaling and root planing alone,

tetracycline fiber therapy along with scaling and root
planing improves periodontal parameters and significantly
reduces bacterial colony count in treatment of chronic
periodontitis.
 Manan Vyas etal 2018
Treatment with tetracycline in
Assessment of adjunct to SRP improves
Tetracycline as an clinical parameters in
Adjunct to Scaling and periodontitis patients as
Root Planing in compared to SRP alone
Periodontitis Patients
SUBGINGIVAL DOXYCYCLINE

A gel system using a syringe with 10% doxycycline (Atridox)

Bacteriostatic agent and has the ability to downregulate MMP’s

A family of zinc dependent enzymes that are capable of

degrading a variety extracellular matrix molecules including
collagens

Biodegradability- 28 days
 Monica Mahajania etal 2018

Effect of Subgingival Doxycycline Placement on Clinical and

Microbiological Parameters in Inflammatory Periodontal
Disease: Both in Vivo and in Vitro Studies

30% doxycycline both in vivo and vitro study has proven

to be an effective antibiotic of choice both clinically and
microbiologically.
 Marwa Madi etal 2018

The anti-inflammatory effect of locally delivered nano-

doxycycline gel in therapy of chronic periodontitis

Treatment with nDOX gel as an adjunct

to SRP had anti-inflammatory effect by
improving both clinical parameters and
inflammatory markers up to three months
period.
Author Conclusion
Larsen T, 1991 The differences were clinically small
but statistically significant reported to
show transient increases in resistance
in oral microbes

Garrett S, 1997 Compared with SRP, the effects of

10% doxycycline gel as monotherapy
on CAL gain and PD reduction were
equivalent

Novak MJ et al, 2008 Results of the study showed that the

combination therapy provided
statistically significantly greater
clinical benefits than control therapy
for all clinical measures at both 3 and
6 months
 SUBGINGIVAL MINOCYCLINE
FDA approved

 A locally delivered, sustained-release form of minocycline

microspheres (Arestin)

 2% minocycline is encapsulated into bioresorbable

microspheres in a gel carrier.

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.

Pragati S, etal; 2009

 Ethyl cellulose film containing 30% of
Minocycline were tested as sustained
release devices.
 The results of this study indicated that
the use of this device may cause
complete eradication of pathogenic flora
from the pocket after 14 days

Pragati S, etal; 2009

Minocycline ointment is a bioabsorbable
sustained delivery system consisting of 2%
minocycline hydrochloride in a matrix of
hydroxyethyl-cellulose, aminoalkyl-
methacrylate, triacetine and glycerine
 Killeen etal 2018

Two-Year Randomized Clinical Trial of Adjunctive

Minocycline Microspheres in Periodontal Maintenance

Scaling and root planning alone, of moderately

inflamed periodontal pockets at 6-month intervals,
produced stable interproximal alveolar bone
height as well as sustained improvements in
probing depths, clinical attachment level, bleeding
on probing over 24 months; minocycline
microspheres were not shown to enhance these
results.
 Sara Abbas etal 2016
Minocycline Ointment as a Local Drug Delivery in the
Treatment of Generalized Chronic Periodontitis - A Clinical
Study

The results demonstrate that there was significant reduction

in the clinical parameters with improvement in the
periodontal status on application of minocycline ointment as
an adjunct to periodontal flap surgery in generalized chronic
periodontitis.
SUBGINGIVAL CHLORHEXIDINE
FDA approved
PerioChip
• Small chip (4.0 × 5.0 × 0.35 mm)
• Biodegradable hydrolyzed gelatin matrix, crosslinked with
glutaraldehyde ; glycerin and water, into which 2.5 mg of
chlorhexidine gluconate has been incorporated

• Drug concentrations in the GCF greater than 100 μg/ml for

at least 7 days
Soskolne WAMet al, 1997
PERIOCOL-CG

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.

Resorb after 30 days; however their coronal

edge degrades within 10 days.

Nanda Kumar PK et al, 2006

 CHLO-SITE
1.5% chlorhexidine of xanthan type (Ghimas
Company, Italy). Xanthan gel is a saccharide
polymer constitutes of a 3-D mesh mechanism

 Degrades within 10-30 days of injection and effective conc of

chlorhexidine established for at least 15 days in the region.

 mucoadhesive

 well tolerated Nanda Kumar PK et al, 2006

 efficient in treatment of periodontal pockets & periimplantitis

Malvika Singh etal 2018

Assessment of efficacy
of chlorhexidine chip as
an adjunct to scaling
and root planning using Local drug delivery
N-benzoylDL-arginine- using chlorhexidine
2-naphthylamide test kit chip enhances the
benefit of SRP in the
treatment of chronic
periodontitis.
SUBGINGIVAL METRONIDAZOLE

A topical medication containing an oil-based

metronidazole 25%(ELYZOL)

Applied in viscous consistency to the pocket, where it is

liquidized by the body heat and then hardens again,
forming crystals in contact with water.
J.‐H. Lin etal 2018
Modulation of periodontitis progression using
pH‐responsive nanosphere encapsulating
metronidazole or N‐phenacylthialzolium bromide

PLGA/chitosan nanospheres encapsulating

metronidazole or PTB showed potential for
modulating periodontitis progression
Author Conclusion
Stelzel M etal, 1996 No significant differences between the two
treatments were detected. Darkfield
microscopy showed a shift toward a
seemingly healthier microflora for both
treatment modalities

Ainamo J et al, 1992 Probing depths were reduced by 1.2 mm

in the gel and 1.5 mm in the scaling
group. At 6 months, the differences
between treatments were statistically but
not clinically significant.
 MF is used as a 1st-line therapy
1% Metformin Gel in pts with overweight or
obesity and diabetes

• Shown to significantly decrease

intracellular ROS and apoptosis Metformin

• Direct osteogenic effect on

osteoblasts Hypoglycemic
effect
• Partially mediated via promotion of
Bone protective
Runx2 and insulin-like growth effect
factor 1 expression.

Zhen D, 2010
 Z. Akram etal 2018
Locally delivered metformin as adjunct to scaling and root
planing in the treatment of periodontal defects: A systematic
review and meta‐analysis

Adjunctive use of metformin delivery in

periodontal treatment appears to be effective
in BD fill, reducing probing depth and gain in
clinical attachment level.
SIMVASTATIN
Widely used to lower cholesterol

Statins- SMV, lovastatin, and pravastatin

Specific competitive inhibitors of 3-hydroxy-2-methyl-glutaryl

coenzyme A (HMG-CoA) reductase

Okuda K et al, 1992

Modulate bone formation by increasing the expression of BMP-2,
inflammation, and angiogenesis [Mundy G et all, 1998]

Assists in bone regeneration[Henwood JM , 1992]

Anti-inflammatory effect when delivered or applied locally

SMV decreased the production of IL-6 and -8[Sakoda et al, 2006]

SMV reduce nuclear factor-kappa B and activator protein 1 promoter

activity in KB cells

At a low conc, SMV exhibits a +ve effect on the proliferation and

osteoblastic differentiation of human PDL cells
 Zohaib Akram etal 2018
Efficacy of statin delivery as an adjunct to scaling and root
planing in the treatment of chronic periodontitis: A
meta‐analysis

Adjunctive statin delivery appears to be effective in reducing

PD, CAL gain, and BD fill in CP
 Khaled Sinjab etal 2016
The Effect of Locally-Delivered Statins on Treating
Periodontal Intrabony Defects: A Systematic Review and
Meta-analysis

adjunctive use of locally delivered statins to mechanical SRP

to be beneficial increasing bone fill percentage. Improved
inflammatory and bleeding control as well as PD reduction
and CAL gain are possible advantages to using these drugs
in treating patients with periodontal intrabony defects.
Bisphosphonates

• Carbon substituted pyrophosphate analogs

• Potent inhibitors of bone resorption and have been effectively
used to treat metabolic bone diseases

Bind to the HA crystals of bone and prevent their dissolution

Also inhibit formation of osteoclasts

Systemically administered bisphosphonates can
induce GI disturbances such as esophagitis,
erosions, and ulcerations. Local drug delivery
avoids most of these problems, by limiting the
drug to the target site (site specific approach)
The influence of local delivery of bisphosphonate on
osseointegration of dental implants
Aya K Khamis etal 2018

The local use of a bisphosphonate appears to favour the

osseointegration of titanium implants in humans.
Author Conclusion

Rocha M et al, 2001 In type-2 diabetic patients, alendronate

induced more improvement in alveolar
bone crest height than control therapy.

Reddy MS et al, 1995 The bisphosphonate had no effect on

the clinical parameters of gingival
Animal study inflammation or plaque. A trend toward
decreased attachment loss and
mobility was observed in favor of the
alendronate group
Meeraw SJ et al, 1999 The results indicate that alendronate
increases early bone formation rate
Animal study around dental implants. Local
application has resulted in greater
bone-to-implant contact

Bindermann et al, 2000 Diff conc of alendronate (0, 1, 5, 20, or

40 mg/ml) was applied to exposed bone
This study implies that topical delivery
of alendronate at the time of surgery
reduces bone loss in periodontal
procedures involving mucoperiosteal
flap surgery. The most effective dose is
200 microg for topical delivery at the
surgical site and 400 microg for distant
sites.
Kaynak D et al, 2000 Local application of the
aminobisphosphonate alendronate can be

Animal study
used as an adjunct in therapy for reducing
bone resorption following surgery. Also be
suggested that even for the surgical
approaches in dentistry where bone graft
materials and/or dental implants are needed
bisphosphonate can be used

Veena et al, 2010 0.1 ml 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.
 Chitosan

 Chitosan is a natural polysaccharide

 It is either partially or fully deacetylated chitin
 Chitin occurs naturally in fungal cell walls and
crustacean shells
 biodegradable and
biocompatible

accelerates
formation of adhesive
osteoblasts

regenerative
antibacterial
effect

hydrophilic
antifungal agent
polysaccharide
 • Inhibits inflammatory cytokine IL-6 production
in human keratinocytes and IL-12 production in
human monocytes.
• Also downregulates expression of TNF-alpha
and IL-6 at the mRNA level.

Inhibits periodontal pathogens such as P.gingivalis and

A.a

Pichayakorn and Boonme, 2013

Significant improvement in all clinical parameters .

All sites (100%) showed a score of ‘0’ for BOP in the test group at
4 weeks. The results were statistically significant.

Conclusion: that chitosan membranes as a form of LDD could be

used as an adjunct to NSPT.

Irfana S. et al, 2016

 Ikinci et al (2002)

Antimicrobial activity of chitosan formulations either in a gel or

film form against P. gingivalis

Promising delivery systems for local therapy of periodontal

diseases due to its antimicrobial activity and bio adhesive property
0.75% BORIC ACID GEL

Boron, a bioactive trace present abundantly in the environment

as boric acid and borate

Borinic acid are quinoline esters, identified class of new

antibacterial compounds that contains boron.

Benkovic SJ etal;2005
inflammatory and immune
response regulation

osteogenesis and the

maintenance of bones

increases glutathione and its analog, and

promotes other neutralizing agents of reactive
oxygen species, thus preventing oxidative
damage
Dharmendra Kanoriya etal 2017
“Clinical efficacy of
subgingivally‐delivered
0.75% boric acid gel as an
adjunct to mechanotherapy
in chronic periodontitis: A
randomized, controlled
clinical trial”
Bori acid as an adjunct
to SRP can provide a
new insight into
therapeutic strategies
for the management of
CP, but further clinical
evaluations are needed
 Sandeep Singhal etal 2017
“Boric acid gel as local drug delivery in the treatment of class II
furcation defects in chronic periodontitis: a randomized,
controlled clinical trial”

The .75% BA group showed significant improvement in

clinical parameters compared to placebo gel as an adjunct to
SRP. This implies an alternative for treatment of class II
furcation.
COMMERCIALLY AVAILABLE LDDs
SOME SYSTEMATIC REVIEWS ON
LOCAL DRUG DELIVERY
PHYTOTHERAPEUTIC AGENTS

Neem

• reduce bacteria and plaque

• effective inhibition of glucosyl transferase activity &

reduced bacterial adhesion to saliva
Vennila K (2016)

10% whole Azadirachtaindica (neem) chip as an adjunct to SRP

& found that clinical parameters were statistically improved and
presence of P. gingivalis strains were significantly reduced in the
neem chip sites
Aloe-vera Cactus plant that belongs to the Liliaceae family.
More than 300 species of aloe plants exist, but only
2 species have been studied, which are Aloe
barbadensis Miller and Aloe aborescens.

Anti-inflammatory, Reduces
Pharmacological actions antibacterial, bleeding,
antioxidant, antiviral inflammation
and antifungal and swelling of
actions the gums.

Antiseptic Healing promoter

Bhat G (2013)

suggested that subgingival administration of Aloe vera

gel results in improvement of periodontal condition.
Aloe vera gel can be used as a local drug delivery
system in periodontal pockets

Jain J (2016)
Concluded aloe vera showed antibacterial property
against A.a, Clostridium bacilli, Strep and Staph
Lemon grass

antiseptic,

antipyretic antiemetic,

anti-
antispasmodic,
rheumatic,

analgesic,
Warad SB et al (2013)
conducted a study to evaluate locally delivered 2% lemongrass oil
in gel form and it was found that it offers a new choice of safe and
effective adjunct to SRP
Green tea
Flavonoids, including catechins, and their derivatives.

Therapeutic effects
antioxidant, anti-collagenase, antiinflammatory, anti-caries,
antifungal, antiviral and antibacterial

• Mageed et al (2015)
alcoholic green tea extract
was able to inhibit and kill
P.gingivalis
The effect of green tea as an adjunct to scaling and root planing
in non-surgical periodontitis therapy: a systematic review

Clinical Oral Investigations

S. J. Gartenmann etal January 2019

The local application of green tea catechin as

an adjunct to SRP may result in a beneficial
reduction in PPD.
Warad SB et al (2013)
conducted a study to evaluate locally delivered 2% lemongrass oil
in gel form and it was found that it offers a new choice of safe and
effective adjunct to SRP

Kudva P et al (2011) evaluated the therapeutic effect of locally delivered

green tea catechin in management of chronic periodontitis and it was

found that green tea adjunct to SRP more effective than SRP alone
Tea tree oil

 derived from the paper bark tea

tree

 broad-spectrum antimicrobial,
antifungal, antiviral, antioxidant
and anti-inflammatory effect

Elgendy EA(2015)suggested that TTO is effective as an

adjunctive treatment of SRP on the clinical parameters and
the level of PTX3 (pentraxin-3) in CP
Curcumin

 Zingiberaceae family

 Active constituents include the three curcuminoids:

Curcumin, demethoxycurcumin, and
bisdemethoxycurcumin
Exhibits anti-inflammatory, antioxidant, anticarcinogenic, antiviral,
and antimicrobial activities.

Modulates the inflammatory response by down-regulating the activity

of COX-2, lipoxygenase, and inducible NO synthase enzymes and
inhibits the prdn of the inflammatory cytokines.

Izui S et al (2015) suggested antibacterial effect of curcumin against

P.gingivalis
 Comparative evaluation of natural curcumin and synthetic
chlorhexidine in the management of chronic periodontitis as a local
drug delivery: A clinical and microbiological study

Anitha V, etal 2019

Although curcumin has equivalent benefit to chlorhexidine,

curcumin being an ayurvedic herb is an excellent alternative to
chlorhexidine due to minimal side-effects
Nagasri M (2013)

found that the local application of curcumin in conjunction with

SRP have showed improvement in periodontal parameters and
has a beneficial effect in patients with CP
Coriander
Umbelliferae family

It has anti-inflammatory, analgesic,

anti-bacterial and anti-oxidant
activities

Yaghini J(2014)

concluded a RCT on effects of subgingival application of

herbal gel (extracts of oak and coriander) in periodontal
pockets showed statistically significant improvements in
periodontal indices.
 Babul

 Babul has cyanogenic glycosides in addition to several

enzymes such as oxidases, peroxidases and pectinases

 Its bark contains tanins (24-42%) which has analegesic, anti-

inflammatory properties

Clark DT et al (1993)
suggest action of acacia gum against suspected periodontal pathogens
like A.a, Capnocytophaga spp., P. gingivalis, P.intermedia, T.denticola
and their enzymes has a clinical value.
 Pomegranate

Polyphenolic flavonoids believed to prevent

gingivitis by reduction of oxidative stress in the
oral cavity, antioxidant activity, anti-inflammatory
effects and anti-bacterial effects
Gomes LA (2016) did a study to evaluate the antimicrobial
activity of pomegranate glycolic extract (PGE) against the
periodontal pathogen P.gingivalis

Phogat M(2014) conducted a RCT to evaluate the efficacy

of a xanthan based chlorhexidine versus herbal gel [Babul,
Bakul, Promogranate] as an adjunct to periodontal therapy
and it was found that there were significant clinical benefits
when compared with SRP alone.
 Local delivery of antimicrobial agents
and periimplant mucositis/implantitis
Author Conclusion

Mombelli et al, 2001 Demonstrated in 25 pts with periimplant

mucositis that there was a significant
reduction of four periopathogenic species,
but other species, such as P. gingivalis
and A.a, had very low baseline and were
not significantly affected. There was a
slight but not significant improvement in
the probing depth at 12 months.
Author Conclusion
Butcher A et al, 2004 Showed significantly greater
probing attachment levels and
lesser PPD and bleeding index than
those who received scaling/root
planing alone

Persson et al, 2006 Implants showed a statistically

significant reduction in both PPD
and percentage of sites with
bleeding on probing between
baseline and day 360
 CONCLUSION

Scaling and root planing alone are effective in reducing pocket

depths, gaining increases in periodontal attachment levels, and
decreasing inflammation levels.

When scaling and root planing are combined with the subgingival
placement of sustained-release vehicles, however, additional
clinical benefits are possible, including further reduction in pocket
depths, additional gain in clinical attachment level and further
decrease in inflammation.
The decision as to when to use local or systemic antimicrobials
should be based on the clinicians consideration of the clinical
findings, the patient’s medical and dental history, patient
preferences, and potential benefits of adjunctive therapy with
these agents.
Other Local Drug Delivery Agents

DENDRIMERS

Polymeric molecules with three dimensional net works

Used mainly in lymphatic drainage

CARBON NANOTUBES

Tube shaped material and made up of carbon.

Mainly used in lung cancer therapy

MONOCLONAL ANTIBODIES

Antibody produced by a single clone of cells or cell line

Used mainly for cancer therapy

Lipid formulations for lymphatic delivery

porous nature of lymphatic vasculature allows hydrophilic

macromolecules and macromolecular conjugates into the
lymphatic system

presence of peyer’s patches in the intestinal wall provide an

entry point for the transport of lipids.
To make use of this, several lipid based formulations such as
lipid nanoemulsions, solid lipid nanoparticles, nano
structured lipid carriers and so on are developed.
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1.Carranza’s clinical periodontology – 11th edition

2.Essentials of clinical periodontology and periodontics; Shantipriya Reddy –

4th edition

3. Clinical Periodontology & Implant Dentistry - Jan Lindhe 5 edition

4. Advanced Drug Delivery Systems in Treating Periodontal Diseases-A

Review; G. Harini, G. Kaarthikeyan; IOSR Journal of Dental and Medical
Sciences Volume 13, Issue 1, Ver. VIII (Feb. 2014), PP 27-32

5. Local drug delivery in periodontics: a strategic intervention; Dr. Vidya

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International Journal of Pharmacy and Pharmaceutical Sciences, Vol 4, Issue
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8. Local Drug Delivery in periodontal diseases. ……A Review; Amitha

Ramesh , Agumbe Priyanka Prakash & Biju Thomas; NUJHS Vol. 6, No.1,
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Nandakumar; Trends Biomater. Artif. Organs, Vol 19(2), pp 74-80 (2006)

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