GOOD MORNING

Dr. Heta Pratik Karani

2
nd
year postgraduate student
MICROBES
SYSTEMIC
FACTORS
HORMONES
STRESS
HOST
RESPONSE
GENETIC
SUSEPTIBILITY
PERIODONTAL
INFECTIONS
LIMITATIONS OF MECHANICAL
DEBRIDEMENT - Quirynen et al (2002)
ANTI MICROBIALS IN PERIODONTAL
DISEASE??

The complex anatomy of the root
Concavities
Lacunae
Dentinal tubules
Invaded soft tissues
Substantial trauma from repeated attempts at
instrumentation in locally unresponsive sites

sites where repeated treatment fails to stop the
disease referred to as refractory subjects or
non-responding sites could be related to the
persistence of pathogens in the pocket after
treatment or to production of specific virulence
factors interfering with the host defense (e.g.
leukotoxin production, encapsulation)

severe or aggressive forms of periodontitis

It is evident that antimicrobial agents are of great
interest & may be valuable as adjuncts to
mechanical therapy.
WHY THE NEED OF LOCAL DRUG
DELIVERY???
Systemic ?? Or local??
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 non treated sites
Clinical Limitations Requires good patient
compliance
Reinfections limited to the treated
site
Diagnostic problems Identification of pathogens,
choice of drug
Distribution pattern of lesion &
pathogens, identification of sites
to be treated
Pain/discomfort Not painful Nil
Drug Dosage Higher drug dosage (mg) Lower Dosage
Peak levels 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
Effects on connective tissue
Associated plaque
Effective Limited
CLASSIFICATION
I ] Based on application [Rams and Slots]

A ] Personally applied

i ] Nonsustained sub gingival drug delivery
Home oral irrigation
Home oral irrigation jet tips
Traditional jet tips
Oral irrigator (water pick)
Soft cone rubber tips (pick pocket)

ii ] Sustained sub gingival drug delivery
None developed

B ] Professionally applied (in dental office)

i ] Nonsustained sub gingival drug delivery
Pocket irrigation

ii ] Sustained sub gingival drug delivery
Controlled release devices
hollow fibres
dialysis tubing
Strips
Film
II ] Based on the duration of medicament release
(Greenstein and Tonetti 2000)

A ] SUSTAINED RELEASE DEVICES Designed
to provide drug delivery for less than 24 hours

B ] CONTROLLED RELEASE DEVICES
Designed to provide drug release that at least
exceeds day or for at least 3 days following
application (Kornman1993)
III ] Based on degradation

A ] Biodegradable
B ] Non biodegradable

IV ] Based on physical form
FIBRES

Hollow
Monofilament

Tetracycline
Chlorhexidine

FILMS

Matrix delivery
systems
Biodegradable
Soluble films
Fish collagen
Dissolution
Steinberg et al
Non biodegradable

Insoluble films
Ethyl cellulose
diffusion
CHX, tetracyclines,
metronidazole
INJECTABLE
SYSTEMS

Easy &
effective

Cost saving
GELS

Solid/semisolid

formulations
Base Methyl
cellulose

CHX,
metronidazole,
tetracycline etc
STRIPS &
COMPACTS

Polymers and
monomers
impregnated
with drug

Metronidazole
CHX,
Augmentin,
Tetracycline,
Doxycycline
VESICULAR
SYSTEMS

Mimic
biomembranes
in terms of
structure ad
bio-behaviour

Triclosan.,
CHX
MICRO
PARTICLE
SYSTEM

Biodegradable
PLA or PGLA

Tetracycline &
doxycycline
microspheres
Minocycline
microspheres
NANO
PARTICULATE
SYSTEM

Targeted
controlled slow
drug release
High
dispersibility in
aqueous
medium
Bioadhesive &
increases
stability
ADVANTAGES OF CONTROLLED DRUG
DELIVERY SYSTEMS
Can attain 100 fold higher concentrations

Can employ agents that are not suitable for systemic administration

Patient compliance

Alternative for patients predisposed to adverse reactions from
systemic antibiotic administration

Reduced risk for drug resistant microbe development at non oral
body sites
(Rams and Slots)
Increased access to the site

Lower total drug dosage (Goodson 1989)
DISADVANTAGES OF CONTROLLED DRUG
DELIVERY SYSTEMS
Difficulty in placing therapeutic concentrations into
deeper part of periodontal pockets and furcation
lesions

Time consuming and labour intensive

Do not have effect on bacteria residing on extra
pocket oral niches

No diagnostic tool is available for mapping sites
with localized organisms for treatment with LDD
INDICATIONS AND CONTRAINDICATIONS
INDICATIONS

As an adjunct to root
surface instrumentation
in pockets of 5 mm or
greater

Localized recurrent
pockets in patients under
supportive periodontal
therapy

Non responding sites to
conventional therapy in
well motivated patients


CONTRAINDICATIONS

Allergic to particular drug used


In pregnant and lactating
mothers (for tetracycline group
of drugs)


To be used with caution in
patients with history of immune
deficiency (to prevent the
overgrowth of candida or other
resistant organisms)

ADVERSE EFFECTS
Allergic reactions

Might produce resistant strains or overgrowth of intrinsically
resistant organisms

Occurrence of candidiasis especially

Pain on insertion

Burning sensation on insertion (with Chlorhexidine)

Development of abscesses

Interference with taste

Tonetti (2000)

DRUG SELECTION
Identification of periodontal pathogens

Is advisable to do bacterial culture and sensitivity
testing - Magnusson 1989
e.g., Tetracyclines often administered, as they are
broad spectrum antibiotics. However studies also
showed patients previously treated with tetracycline
responded not well and other antibiotics were
beneficial

No single drug is the universal drug of choice.
VARIOUS DRUGS USED AS
CONTROLLED RELEASED SYSTEMS
Tetracycline
Doxycycline
Metronidazole
Chlorhexidine
Minocycline
Ofloxacin
Others

TETRACYCLINE :
Broad spectrum antibiotic - activity against both
gram +ve and gram -ve organisms

Consist of four fused cyclic rings and the various
derivatives consist of only minor alterations of the
chemical constituents attached to this basic ring
structure

Tetracycline, Doxycycline and Minocycline are
commonly used with similar spectrum of activity.
Hence resistance to one indicates resistance to all
the three

They are bacteriostatic agents but may have a
bactericidal effects in high concentrations (Walker
1996). These drugs principally acts by inhibiting
protein synthesis

In addition to its antibacterial action, it also
demineralizes cementum and dentin, when applied
topically thereby enhancing attachment of fibroblasts
to the tooth surface
(Wikesjo et al 1986; Morrison et al 1992)
ADVANTAGES :

Has high substantivity i.e. after local delivery, it has
been detected at 1-20 m within epithelial tissues
(Ciancio et al 1992)

Detectable in crevicular fluid several weeks following
application (Wikesjo et al 1986)

Attains high concentration in crevicular fluid
TETRACYCLINE FIBRES (ACTISITE)
They are non-resorbable cylindrical drug delivery
devices made of a biologically inert, plastic co-polymer
loaded with 25% tetracycline HCL powder
(Goodson et al 1983)

23 cm in length and 0.5 mm in diameter. The fibre is
flexible and can be folded on itself to nearly fill the pocket

Able to release and maintain tetracycline for a period of 7
days (Tonetti et al 1990) with mean concentrations of 43
g/ml in the superficial portions of the pocket wall

At a concentration more than 150 times achieved by
systemic tetracycline, these fibres provide bactericidal
concentration of tetracycline.
TYPES OF FIBRES
Hollow fibres:
Cellulose acetate fibres are filled with tetracycline and they
provide only sustained release system

Monolithic fibres:
Prepared by melt extrusion technique, wherein, a mixture of 25%
tetracycline HCl and 75% ethylene vinyl acetate was heated to
214
0
C and extruded as 0.5 mm fiber and they provide a controlled
release system (Goodson et al 1985)

Resorbable fibres:
Minabe (1989) described a device in which tetracycline is
incorporated into cross-linked collagen matrix, capable
of delivering tetracycline in the crevicular fluid at therapeutic levels
for upto 10 days after insertion and drug levels ranged from 17 to
180g/ml.
TECHNIQUE
An individual or several teeth can be treated at a
time

Short lengths of fibre, 2-3 inches are taken in a
cotton forceps and placed at the opening of the
pocket to be treated

The fibre folded on itself

The folding procedure might be repeated until all the
pockets are nearly filled

Interproximal pockets should be packed from both the
buccal and the lingual sides

After placement, the area is isolated with cotton rolls or
gauze, tooth dried with the air syringe and a drop of
tissue adhesive applied at each interdental area as well
as facially and lingually

Alternatively, periodontal pack can be placed (Goodson
et al 1985)

Fibres should be in place for 7-14 days

Fibre removal (in case of non-resorbable fibres) is fairly
simple. They can be teased out of the pockets with a
curette
INSTRUCTIONS TO BE GIVEN TO THE
PATIENT
Not to brush or floss the treated areas until fibres are
removed

To rinse with chlorhexidine mouth rinse while the fibres
are in place and for 1 week after their removal

Advised to return back to normal original oral hygiene
procedure after 1 week or after fibre removal (in case
of non-resorbable fibres)

To come for recall visit at 4-6 weeks
Recently bioresorbable tetracycline fiber has
been developed with base of collagen film,
which is commercially available as
PERIODONTAL PLUS AB.
No second appointment for removal as it
biodegrades within 7 days.
Can be concluded that local delivery of tetracycline
improves the clinical outcomes of traditional
treatment and should be considered particularly as
an adjunct to scaling root planing. Considerations
regarding the adverse effects of widespread use of
tetracycline should be taken into account when
choosing a therapeutic strategy of chronic
periodontitis
Pavia et al (2003)

VARIOUS DRUGS USED AS
CONTROLLED RELEASED SYSTEMS
Tetracycline
Doxycycline
Minocycline
Metronidazole
Chlorhexidine
Ofloxacin
Others

DOXYCYCLINE POLYMER (ATRIDOX)
A biodegradable formulation containing
10% by weight doxycycline,
33% by weight poly (DL-Lactide) and
57% by weight N-methyl 2-pyrrolidone
was developed

MECHANISM OF ACTION :
Activity against putative periodontal pathogens and
effective in the management of periodontal diseases
(Golub et al 1984, McCulloch et al 1990)

It is a liquid biodegradable system that hardens when
placed in periodontal pocket
TECHNIQUE
Liquid delivery system containing 10% doxycycline
hyclate is contained within a syringe that has a blunt
ended 23 gauge cannula attached. The cannula has
a diameter of a periodontal probe




The tip of the cannula is introduced to the depth of
the pocket and the drug is expressed out
As it begins to harden on contact with the moisture
and during the 1-2 minutes of hardening, it is packed
into the pocket using the underside of the moistened
curette or other blunt-ended instrument

Immediately after administration, the polymer slightly
protrudes from the pocket orifice

Periodontal dressing or adhesive is used as an aid
in retention of the system

Instructions given to the patient is in lieu with
tetracycline fibres
VARIOUS DRUGS USED AS
CONTROLLED RELEASED SYSTEMS
Tetracycline
Doxycycline
Minocycline
Metronidazole
Chlorhexidine
Ofloxacin
Others

MINOCYCLINE
(DENTOMYCINE AND PERIOCLINE)
3 modes of local application are available:
film
microspheres
ointment
It is a bacteriostatic


Film
Ethylcellulose containing 30% of minocycline cast
from ethanol, chloroform or chloroform with
polyethylene glycol were tested as sustained
release devices (Elkayam et al)

The results of this study indicated that the use of this
device may cause complete eradication of
pathogenic flora from the pocket

Microspheres:
Minocycline micro-encapsulated in a resorbable poly
glycolide-lactide slow release polymer (Braswell et
al) can be administered by means of disposable
plastic syringe.
The volume of microspheres in each syringe is 4 mg
which is equivalent to 1 mg of minocycline base

Microspheres :
Injected into the pocket

Adhered to the soft tissue

Dissolves

Releases minocycline in sustained manner
Once in the pocket the micospheres react with the
crevicular fluid which hydrolyzes the polymer causing
water-filled channels to form inside the microspheres

These holes become the pathway for the antibiotic for
sustained release

The minocycline then diffuses through these portals and
permeates the surrounding tissues

Over a period of time, the microspheres themselves get
fragmented through polymer hydrolysis and degrade and
are ultimately bioresorbed.

It is reported that the microspheres are completely
biodegraded in about 21 days
Ointment:
It is a light yellow colored ointment base of

20 mg hydroxyethyl cellulose,
10 mg eudragit RS,
60 mg triacetine and
glycerine 0.5 g

supplied in a disposable polypropylene applicator and
each applicator contains the equivalent of 10 mg
minocycline in 0.5 g ointment

Repeated applications of 2% minocycline, 1 application
per week for 4 weeks, 2 applications at intervals of 1 or 2
weeks, 3 applications at 2 weekly intervals were effective
Thus, minocycline can be used as a adjunct to
mechanical debridement with improved
effectiveness for treatment of chronic periodontitis

Vanderkerckhove et al
VARIOUS DRUGS USED AS
CONTROLLED RELEASED SYSTEMS
Tetracycline
Doxycycline
Minocycline
Metronidazole
Chlorhexidine
Ofloxacin
Others

METRONIDAZOLE
A 5-nitroimidazole compound specifically targets
anaerobic microbes but its hydroxyl metabolite
enhances its effect even against other group of bacteria
(Pavicic et al)

Upon entry into an organism, metronidazole is reduced
at 5-nitro position by electron transport proteins
producing free radicals. These react with bacterial DNA
causing cell death. Hence it is primarily a bactericidal
agent (Drisko et al).

Serum concentration of Metronidazole has shown to
attain MIC levels for most periodontal pathogens (Brit
and Prohlod 1986) and it is found to eliminate
spirochetes from ANUG lesions.
METRONIDAZOLE DENTAL GEL
(ELYZOL)
Resorbable

Consists of 25 % of Metronidazole benzoate in a
matrix consisting of
Glyceryl mono-oleate
Sesame oil

The gel is subgingivally placed with a syringe and a
blunt cannula. The drug concentration in crevicular
fluid follows an exponential pattern which is
compatible with sustained drug delivery
Thus metronidazole is effective as an adjunct to
SRP in the treatment of chronic adult periodontitis,
but clinical significance and dissemination of
antibiotics should be taken into account in the
evaluation of metronidazole as an alternative to
SRP
(Pavia et al 2004)

VARIOUS DRUGS USED AS
CONTROLLED RELEASED SYSTEMS
Tetracycline
Doxycycline
Minocycline
Metronidazole
Chlorhexidine
Ofloxacin
Others

CHLORHEXIDINE
It is a topical antiseptic belonging to the family of
bisguanides. It is mainly active against gram +ve
organisms

It is bacteriostatic at lower and bactericidal at higher
conc.

It has been detected in excess of 125 g/ml in
crevicular fluid for 1 week following a single
application (Soskolne et al 1998)
CHLORHEXIDINE CHIP (PERIOCHIP)
It is a bio absorbable device

Comprises of 34% Chlorhexidine in a cross linked
gelatin matrix

Chip is 5 mm long, 4 mm wide with 2.5 mg of
chlorhexidine gluconate
TECHNIQUE
After scaling and root planing, the chip is grasped in a
cotton forceps and gently inserted into the pocket

It is advisable to dry the area before placing the chip

As burning sensation is reported after the chip
placement, placement of multiple chips around a single
tooth may result in discomfort

The chip degrades in a period of 7-10 days and
requires no retentive system

Instructions given to the patient is in lieu with
tetracycline fibres
Periocol-CG (Eucare)
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.
Collagen is a natural protein, which is chemotactic for fibroblasts,
enhances fibroblast attachment via its scaffold like fibrillar structure
and stimulates platelet degranulation, thereby accelerating fibers
and clot attachment. It has been shown to resorb after 30 days;
however their coronal edge degrades within 10 days.





Chlo-Site
Chlo-Site is an agent containing 1.5% chlorhexidine of xanthan type
(Ghimas Company, Italy). Xanthan gel is a saccharide polymer, which
constitutes of a three-dimensional mesh mechanism, which is
biocompatible with chlorhexidine.
Contemp Clin Dent. 2013 Apr-Jun; 4(2): 156161.
doi: 10.4103/0976-237X.114848
PMCID: PMC3757875
Comparison of the efficacy of chlorhexidine varnish and chip in the treatment of
chronic periodontitis
B. S. Jagadish Pai, Smitha Anitha Rajan, M. Srinivas, R. Padma, Girish Suragimath, Amit Walvekar, Saakshi Goel, andVinesh
Kamath
Background:
The purpose of this study was to clinically evaluate the benefits of sub gingival chlorhexidine
(CHX) varnish and biodegradable CHX chip application used as an adjunct to scaling and root
planning (SRP) as combined therapy and also to compare the effect of combined therapy with
SRP alone.
Materials and Methods:
Fifteen patients with at least three sites with a probing pocket depth (PPD) of 5-8 mm were considered.
Following baseline evaluation, all three sites were subjected for SRP. After completing SRP, each site was
randomly subjected for CHX varnish, CHX chip application and the 3
rd
site was left without any medication as a
control. Clinical parameters such as sulcus bleeding index, plaque index, bleeding on probing (BOP), PPD, and
clinical attachment level (CAL) were recorded at baseline, 1 month and 3 months post-operatively.
Results:
All three groups presented with an improvement in clinical parameters compared to baseline. The mean
reduction in PPD was 2.4 mm in SRP sites, 2.5 mm in SRP + CHX varnish sites and 2.8 mm in SRP + CHX
chip sites. The mean gain in CAL was 2.4 mm in SRP sites, 2.3 mm in SRP + CHX varnish sites and 2.8 mm
SRP + CHX chip sites.
Interpretation and Conclusion:
The present study indicated that application of CHX varnish and placement of CHX chip as an
adjunct to SRP produced a clinically significant reduction in the PPD, BOP and a gain in CAL at
30
th
day and 90
th
day from baseline when compared to SRP alone. The results though were not
statistically significant

VARIOUS DRUGS USED AS
CONTROLLED RELEASED SYSTEMS
Tetracycline
Doxycycline
Minocycline
Metronidazole
Chlorhexidine
Ofloxacin
Others

OFLOXACIN
Ofloxacin belongs to quinolone family which
constitute a group of 1,8 naphthyridine derivatives
and are synthetically produced drugs

They are considered to be bactericidal as they
inhibit the enzyme DNA replication by acting on the
enzyme DNA gyrase. The bactericidal effect can
only occur in the presence of competent RNA and
protein synthesis. The imbalance of inhibited DNA
replication and continued protein synthesis results
in inhibition of cell division

OFLOXACIN INSERTS (PT-01)
Okade and co-workers
PT-01 is a soluble insert, with both fast and
sustained release parts containing 10% ofloxacin
and showed a constant drug level of above 2 mg/ml,
(minimum MIC for most pathogenic organisms)
which could be sustained for up to 7 days

The controlled release system exhibited a biphasic
pattern with a rapid early release phase peaking at
approximately 12g/ml and stabilizing at
approximately 2g/ml from day 3 to 7 following
insertion (Higashi et al 1990)
Initial investigations failed to any additional
microbiological effect in a split mouth design
(Kimura et al 1991)

Further investigations by Yamagami et al (1992)
showed four weekly applications of the insert
resulted in significant resolution of periodontal
inflammation and improvement in other clinical
parameters.
COMPARISON OF DRUGS USED FOR LOCAL
DELIVERY
FUTURE TRENDS
CLARITHROMYCIN GEL
A study has been conducted to investigate the adjunctive effects of subgingivally
delivered 0.5 % clarithromycin as an adjunct to scaling and root planing for treating
chronic periodontitis smoker subjects.
At the end of 6 months, the mean GI, PI, SBI, PPD, CAL for the clarithromycin group
was significantly reduced. This product is still under investigation and yet to be
patented.

HERBAL PRODUCTS
Various herbal formulations like aloe vera, neem, tulsi, propolis, cocoa husk,
pomegranate, cranberry etc. are being used widely these days. These products have
shown promising results with no side effects and are economical as well.


FIBROBLAST GROWTH FACTOR would 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 growth factor (bFGF) in a controlled-release
system was developed. This sandwich membrane induced
successful regeneration of the periodontal tissues in a short
period of time (4 weeks)

COLLOIDAL DRUG CARRIERS include micelles,
emulsions, liposomes and nanoparticles (nanospheres and
nanocapsules). It is noteworthy that only liposomes and
nanoparticles have been largely exploited for drug delivery
because the methods of preparation are generally simple
and easy to scale-up. The aim of using colloidal carriers is
generally, to increase specificity towards cells or
tissues, to improve bioavailability of drugs by increasing
their diffusion through biological membranes and/or to
protect them against enzyme inactivation.
NANOPARTICLES, owing to their small size,
penetrate regions that may be inaccessible to other
delivery systems. These systems reduce the
frequency of administration and further provide a
uniform distribution of the active agent over an
extended period of time.
Three preliminary studies have been conducted
a) Dung et al used Antisense oligonucleotide- loaded
chitosantripolyphosphate (TPP) nanoparticles and showed the
sustained release of oligonucleotides which is suitable for the local
therapeutic application in periodontal diseases

b) Pinon et al conducted a preliminary 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.

c) Moulari et. al, investigated 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. HLE-loaded PLGA nanoparticles were prepared using
interfacial polymer deposition following the solvent diffusion method.
Incorporation of the HLE into a colloidal carrier improved its
antibacterial performance and diminution of the bactericidal
concentration was observed.

Tetracycline, minocycline and metronidazole as an
adjunct to scaling and planing compared with
scaling and planing alone
(Radvar et al 1996; Kinane et al 1999)

Both the studies showed all the 3 drug delivery
systems provided some benefit beyond scaling and
planing. However, only tetracycline fibers
demonstrated a significant advantage over scaling
and planing in the treatment of persistent
periodontal lesions
Journal of Periodontology January 2013, Vol. 84, No. 1, Pages 24-31 , DOI 10.1902/jop.2012.110721
(doi:10.1902/jop.2012.110721)

Efficacy of Subgingivally Delivered Simvastatin in the
Treatment of Patients With Type 2 Diabetes and Chronic
Periodontitis: A Randomized Double-Masked Controlled
Clinical Trial
A.R. Pradeep,
*
Nishanth S. Rao,
*
Pavan Bajaj,
*
and Minal Kumari
*
*Department of Periodontics, Government Dental College
and Research Institute, Bangalore, India.

Background: Simvastatin (SMV) is a specific competitive inhibitor of 3-hydroxy-2-methyl-glutaryl
coenzyme A reductase. Recently, it has been reported that statins promote bone formation. The
present study is designed to investigate the effectiveness of 1.2% SMV in an indigenously
prepared, biodegradable, controlled-release gel as an adjunct to scaling and root planing (SRP) in
the treatment of patients with type 2 diabetes and chronic periodontitis (CP).
Methods: Thirty-eight patients were categorized into two treatment groups: SRP plus 1.2% SMV
and SRP plus placebo. Clinical parameters were recorded at baseline before SRP and at 3, 6,
and 9 months; they included modified sulcus bleeding index (mSBI), probing depth (PD), and
clinical attachment level (CAL). At baseline and after 6 and 9 months, radiologic assessment of
intrabony defect (IBD) fill was done using computer-aided software.
Results: Mean PD reduction and mean CAL gain were found to be greater in the SMV group than
the placebo group at 3, 6, and 9 months. Furthermore, significantly greater mean percentage of
bone fill was found in the SMV group (32.64% 12.90%) compared to the placebo group (4.22%
9.75%) after 9 months.
Conclusion: There was a greater decrease in mSBI and PD and more CAL
gain with significant IBD fill at sites treated with SRP plus locally delivered
SMV in patients with type 2 diabetes and CP.

J Clin Diagn Res. 2013 October; 7(10): 23302333.
Published online 2013 October 5. doi: 10.7860/JCDR/2013/5793.3517
PMCID: PMC3843431
Clinical Effects of Subgingivally Delivered Spirulina Gel in Chronic
Periodontitis Cases: A Placebo Controlled Clinical Trial
Jaideep Mahendra,
1
Little Mahendra,
2
Jananni Muthu,
3
Libby John,
4
and Georgios E. Romanos
5

Aims and Objectives: The aim of this study was to assess the clinical effects of
Spirulina in-situ gel as an adjunct to Scaling And Root Planning (SRP) in the treatment
of chronic periodontitis subjects.
Material and Methods: 64 sites were selected with probing pocket depth of 5mm and
they were divided into 2 groups; 33 sites were treated with SRP along with spirulina gel
(Group A) and 31 sites were treated with SRP alone (Group B). Clinical parameters
were recorded at baseline before SRP and at 120
th
day after the treatment therapy.
The parameters included Probing Pocket Depth (PPD) and Clinical Attachment Level
(CAL).
Results: Both the groups showed significant improvement in the parameters.
However, Group A (SRP along with spirulina) showed statistically significant decrease
in mean probing pocket depth and gain in the clinical attachment level after 120 days
as compared to Group B SRP alone.
Conclusion: Locally delivered spirulina gel, along with scaling and root
planning, has been shown to cause a beneficial impact. The efficacy of the product
as a local drug delivery system in the non-surgical treatment of periodontitis without
any side effects has been proved. Spirulina appears to be promising. It exerts strong
anti-inflammatory effects which are closely connected with its antioxidative activity.
J Indian Soc Periodontol. 2013 Mar-Apr; 17(2): 198203.
doi: 10.4103/0972-124X.113069 PMCID: PMC3713751
Green tea extract as a local drug therapy on periodontitis patients with diabetes mellitus: A randomized
casecontrol study
Jayaprakash S. Gadagi, Vijay K. Chava,
1
and Venkata Ramesh Reddy
Background:
The green tea extract is a naturally occurring product having beneficial effects that counteract with the
pathobiological features of periodontitis and diabetes mellitus. Hence, the present study was aimed at
incorporation of green tea extract into hydroxylpropyl methylcellulose and investigates its efficacy in
chronic periodontitis patients associated with and without diabetes mellitus.
Materials and Methods:
For the in vitro study, formulation of green tea strips and placebo strips, and analysis of drug release pattern
from the green tea strips at different time intervals were performed. For the in vivo study, 50 patients (20-65
years), including 25 systemically healthy patients with chronic periodontitis (group 1) and 25 diabetic patients
with chronic periodontitis (group 2) were enrolled. In each patient, test and control sites were identified for the
placement of green tea and placebo strips, respectively. Gingival Index (GI), Probing Pocket Depth (PPD), and
Clinical Attachment Level (CAL) were examined at baseline, first, second, third, and fourth weeks.
Microbiological analysis for Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans was
performed at baseline and fourth week.
Results:
The in vitro study showed 10.67% green tea release at 30 min; thereafter, a slow release was noted till 120
min. In vivo study: Both groups showed significant reduction in GI scores at the test sites. Group 1 showed
significant (P < 0.001) PPD reduction at different time intervals at the test sites. However, group 2 showed
significant reduction from baseline (5.30 0.70) to fourth week (3.5 0.97). Statistically significant gain in CAL
at the test sites was observed both in group 1 (1.33 mm) and group 2 (1.43 mm). The prevalence of P.
gingivalis in group 1 test sites was significantly reduced from baseline (75%) to fourth week (25%).
Conclusions:
Local drug delivery using green tea extract could be used as an adjunct in the treatment of chronic
periodontitis in diabetic and non-diabetic individuals.

ANTIBIOTIC RESISTANCE ASSOCIATED
WITH
LOCAL DRUG DELIVERY SYSTEMS
Local drug delivery provides a high drug
concentration at a specific site

Sublethal amounts of administered drugs leak out of
pockets during therapy. Therefore, the potential exists
that local drug delivery may contribute to
development of drug resistant organisms in areas
other than the treated sites
Exposure to sub inhibitory concentrations of
metronidazole or minocycline resulted in
development of resistance among
P.gingivalis,
P.intermedia,
F.nucleatum and
P.anaerobius
Walker et al, Larsen et al

This suggests that repeated use of these agents
can result in increased levels of drug resistant
bacteria

Thus, it can be concluded local delivery systems
are logical adjuncts for the treatment of a few,
localized non-responding sites, and systemic
delivery reserved to control infections at multiple
sites in patients with persistent disease and for
treating atypical and aggressive forms of
periodontitis
(Tonetti 2000)

DISEASES THAT CAN BE TREATED WITH
LOCAL DRUG DELIVERY SYSTEMS
All drugs were used to treat patients with chronic periodontitis

Only tetracycline fibres and metronidazole were used to treat aggressive
periodontitis

Mandell 1986 - Tetracycline fibers were not efficient in suppressing Aa
in J P
Mombelli et al (1997) - Tetracycline fibers were able to suppress, but not
eliminate Aa
Riep et al (1996) - Local delivery of metronidazole too is not effective at
suppressing Aa levels

These findings need to be considered when treating patients with these
aggressive forms of disease, as they might harbor increased levels of these
organisms.
Thus, at present there is no concrete evidence
to use local delivery agents in the treatment of
aggressive periodontal diseases
J Clin Periodontol. 2013 Mar;40(3):227-41. doi: 10.1111/jcpe.12026. Epub 2013 Jan 16.
A systematic review on the effects of local antimicrobials as adjuncts to
subgingival debridement, compared with subgingival debridement alone, in the
treatment of chronic periodontitis.
Matesanz-Prez P, Garca-Gargallo M, Figuero E, Bascones-Martnez A, Sanz M, Herrera D.
AIMS:
To update the existing scientific evidence on the efficacy of local antimicrobials as adjuncts to
subgingival debridement in the treatment of chronic periodontitis.
MATERIAL AND METHODS:
Fifty-six papers were selected, reporting data from 52 different investigations. All the studies reported changes in
probing pocket depth (PPD) and clinical attachment level (CAL) and most in plaque index (PlI) and/or bleeding
on probing (BOP). Meta-analyses were performed with the data retrieved from the studies fulfilling the inclusion
criteria.
RESULTS:
The overall effect of the subgingival application of antimicrobials was statistically significant (p = 0.000) for both
changes in PPD and CAL with a weighted mean difference (WMD) of -0.407 and -0.310 mm respectively. No
significant differences occurred for changes in BOP and PlI. Subgingival application of tetracycline fibres,
sustained released doxycycline and minocycline demonstrated a significant benefit in PPD reduction (WMD
between 0.5 and 0.7 mm). The rest of the tested outcomes demonstrated a high heterogeneity.
The local application of chlorhexidine and metronidazole showed a minimal effect when compared with placebo
(WMD between 0.1 and 0.4 mm).
CONCLUSIONS:
The scientific evidence supports the adjunctive use of local antimicrobials to debridement in deep
or recurrent periodontal sites, mostly when using vehicles with proven sustained release of the
antimicrobial

REMEMBER..
There is no single universal drug that would be
effective in all situations

Local drug delivery often appears to be as effective
as scaling and root planing with regards to reducing
signs of periodontal inflammatory diseases

Local delivery may be an adjunct to conventional
therapy. The sites most likely to be responsive to
this adjunctive treatment method may be refractory
or recurrent periodontitis
REMEMBER..
At present, there are insufficient data to indicate that one
local drug delivery service is clearly superior to all the
other systems

There is a lack of data to support the impression that
local drug delivery in conjunction with root planing
reduces the need for periodontal surgery more than
scaling and root planing alone.

Should not be substituted for oral hygiene procedures.

Cigarette smoking has a negative influence on outcome
of local drug therapy (Kinane et al 1999)
CONCLUSION
The number of problems encountered in delivering the drugs
to the intended target site with the right dosage is a challenge
to the clinician since drugs often have limited solubility, suffer
breakdown before they reach their target tissues and might
cause unintentional damage to the healthy tissues

Therefore, the nanoparticle based drugs may be ideal to
meet up these challenges

It has been claimed that benefits of nanoparticle based drug
delivery systems have high stability than conventional
delivery mechanisms

Therefore, the introduction of nanoparticle delivery system
has been tried & has gained popularity
CONCLUSION
Various drug delivery and drug targeting systems are
currently under development to obtain

Increased dissolution velocity
Increased saturation solubility
Improved bioadhesivity and
Versatility in surface modification

so that better and effective administration of desired
and newer drug can be done through the best
possible system

Long term longitudinal studies to be done to know the
durability of these drugs on long term basis
REFERENCES
1. Clinical periodontology carranza
2. Jan Lindhe
3. Dental Clinics of North America January 2010 volume 54
number 1
4. Controlled drug release in Periodontics. A review of new
therapies. British Dental Journal 1991;170:405-07.
5. William J. Killoy - Assessing the effectiveness of locally
delivered chlorhexidine in the treatment of Periodontitis.
JADA1999;130: 567-70.
6. Stabholz A, Sela M.N. Friedman M, Golomb G and Soskolne
A - Clinical and microbiological effects of sustained release
chlorhexidine in periodontal pockets. J Clin Periodontol 1986;13:
783-88.
7. Internet sources
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