Local Drug Delivery by Heta

8/12/2019 Local Drug Delivery by Heta

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GOOD MORNING


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LOCAL DRUG DELIVERY

Dr. Heta Pratik Karani2ndyear postgraduate student


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MICROBES

SYSTEMICFACTORS

HORMONES

STRESS HOSTRESPONSE

GENETICSUSEPTIBILITY

PERIODONTALINFECTIONS


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LIMITATIONS OF MECHANICALDEBRIDEMENT - Quirynen et al 2002)

ANTIMICROBIALS IN PERIODONTAL

DISEASE??


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The complex anatomy of the rootConcavities

Lacunae

Dentinal tubules

Invaded soft tissues


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Substantial trauma from repeated attempts atinstrumentation in locally unresponsive sites

sites where repeated treatment fails to stop thedisease referred to as refractory subjects ornon-responding sites could be related to thepersistence of pathogens in the pocket after

treatment or to production of specific virulencefactors interfering with the host defense (e.g.leukotoxin production, encapsulation)

severe or aggressive forms of periodontitis

It is evident that antimicrobial agentsare of greatinterest & may be valuable as adjuncts to

mechanical therapy.


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WHY THE NEED OF LOCAL DRUG

DELIVERY???


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Systemic ?? Or local??ISSUE SYSTEMIC LOCAL

Route of administration Oral/ parentral Site specificDrug 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 patientcompliance Reinfections limited to the treatedsite

Diagnostic problems Identification of pathogens,

choice of drug

Distribution pattern of lesion &

pathogens, identification of sites

to be treatedPain/discomfort Not painful Nil

Drug Dosage Higher drug dosage (mg) Lower Dosage


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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


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CLASSIFICATIONI ] Based on application [Rams and Slots]

A ] Personally applied

i ] Nonsustained sub gingival drug delivery

Home oral irrigationHome 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


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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


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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)


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III ] Based on degradation

A ] BiodegradableB ] Non biodegradable

IV ] Based on physical form


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FIBRES

Hollow

Monofilament

Tetracycline

Chlorhexidine

FILMS

Matrix deliverysystems

BiodegradableSoluble films

Fish collagen

Dissolution

Steinberg et al

Non biodegradable

Insoluble filmsEthyl cellulose

diffusion

CHX, tetracyclines,

metronidazole

INJECTABLESYSTEMS

Easy &effective

Cost saving

GELS

Solid/semisolid

formulations

BaseMethylcellulose

CHX,metronidazole,tetracycline etc


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STRIPS &COMPACTS

Polymers andmonomers

impregnatedwith drug

MetronidazoleCHX,

Augmentin,Tetracycline,Doxycycline

VESICULARSYSTEMS

Mimicbiomembranes

in terms ofstructure ad

bio-behaviour

Triclosan.,CHX

MICROPARTICLESYSTEM

BiodegradablePLA or PGLA

Tetracycline &

doxycyclinemicrospheresMinocycline

microspheres

NANOPARTICULATE

SYSTEM

Targetedcontrolled slowdrug release

Highdispersibility in

aqueousmedium

Bioadhesive &increasesstability


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ADVANTAGES OF CONTROLLED DRUGDELIVERY 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 fromsystemic antibiotic administration

Reduced risk for drug resistant microbe development at non oralbody sites

(Rams and Slots) Increased access to the site

Lower total drug dosage (Goodson 1989)


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DISADVANTAGES OF CONTROLLED DRUGDELIVERY SYSTEMSDifficulty 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


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INDICATIONS AND CONTRAINDICATIONS

INDICATIONS

As an adjunct to rootsurface instrumentationin pockets of 5 mm orgreater

Localized recurrentpockets in patients undersupportive periodontaltherapy

Non responding sites toconventional therapy inwell motivated patients

CONTRAINDICATIONS

Allergic to particular drug used

In pregnant and lactatingmothers (for tetracycline groupof drugs)

To be used with caution inpatients with history of immunedeficiency (to prevent theovergrowth of candida or otherresistant organisms)


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ADVERSE EFFECTSAllergic reactions

Might produce resistant strains or overgrowth of intrinsicallyresistant organisms

Occurrence of candidiasis especially

Pain on insertion

Burning sensation on insertion (with Chlorhexidine)

Development of abscesses

Interference with taste

Tonetti (2000)


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DRUG SELECTION Identification of periodontal pathogens

Is advisable to do bacterial culture and sensitivity

testing - Magnusson 1989

e.g., Tetracyclines often administered, as they arebroad 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.


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VARIOUS DRUGS USED ASCONTROLLED RELEASED SYSTEMS Tetracycline

Doxycycline

Metronidazole

Chlorhexidine

Minocycline

Ofloxacin

Others


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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 ringstructure


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Tetracycline, Doxycycline and Minocycline arecommonly used with similar spectrum of activity.Hence resistance to one indicates resistance to all

the three

They are bacteriostatic agents but may have abactericidal effects in high concentrations (Walker

1996). These drugs principally acts by inhibitingprotein synthesis

In addition to its antibacterial action, it also

demineralizes cementum and dentin, when appliedtopically thereby enhancing attachment of fibroblaststo the tooth surface

(Wikesjo et al 1986; Morrison et al 1992)


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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


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TETRACYCLINE FIBRES ACTISITE) They are non-resorbable cylindrical drug delivery

devices made of a biologically inert, plastic co-polymerloaded with 25% tetracycline HCL powder(Goodson et al 1983)

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

Able to release and maintain tetracycline for a period of 7days (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 bysystemic tetracycline, these fibres provide bactericidal

concentration of tetracycline.


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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

2140

C and extruded as 0.5 mm fiber and they provide a controlledrelease system (Goodson et al 1985)

Resorbable fibres:

Minabe (1989) described a device in which tetracycline is

incorporated into cross-linked collagen matrix, capableof delivering tetracycline in the crevicular fluid at therapeutic levels

for upto 10 days after insertion and drug levels ranged from 17 to

180g/ml.


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TECHNIQUEAn 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


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INSTRUCTIONS TO BE GIVEN TO THEPATIENTNot to brush or floss the treated areas until fibres are

removed

To rinse with chlorhexidine mouth rinse while the fibresare 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 caseof non-resorbable fibres)

To come for recall visit at 4-6 weeks


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Recently bioresorbable tetracycline fiber hasbeen 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.


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Can be concluded that local delivery of tetracycline

improves the clinical outcomes of traditionaltreatment 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 whenchoosing a therapeutic strategy of chronic

periodontitis

Pavia et al (2003)


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Doxycycline

Minocycline

Metronidazole

Chlorhexidine

Ofloxacin

Others


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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


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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 ofthe pocket and the drug is expressed out

A it b i t h d t t ith th i t


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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


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Doxycycline

Minocycline

Metronidazole

Chlorhexidine

Ofloxacin

Others


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MINOCYCLINEDENTOMYCINE AND PERIOCLINE) 3 modes of local application are available:

film

microspheres

ointment

It is a bacteriostatic

Film


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Film

Ethylcellulose containing 30% of minocycline cast

from ethanol, chloroform or chloroform with

polyethylene glycol were tested as sustainedrelease devices (Elkayam et al)

The results of this study indicated that the use of thisdevice may cause complete eradication of

pathogenic flora from the pocket

Mi h


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Microspheres:

Minocycline micro-encapsulated in a resorbable poly

glycolide-lactide slow release polymer (Braswell et

al) can be administered by means of disposableplastic syringe.

The volume of microspheres in each syringe is 4 mg

which is equivalent to 1 mg of minocycline base


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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


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Once in the pocket the micospheres react with thecrevicular fluid which hydrolyzes the polymer causingwater-filled channels to form inside the microspheres

These holes become the pathway for the antibiotic forsustained release

The minocycline then diffuses through these portals andpermeates the surrounding tissues

Over a period of time, the microspheres themselves get

fragmented through polymer hydrolysis and degrade andare ultimately bioresorbed.

It is reported that the microspheres are completely

biodegraded in about 21 days


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Thus, minocycline can be used as a adjunct to

mechanical debridement with improved

effectiveness for treatment of chronic periodontitis

Vanderkerckhove et al


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Doxycycline

Minocycline

Metronidazole Chlorhexidine

Ofloxacin

Others


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METRONIDAZOLEA 5-nitroimidazole compound specifically targets

anaerobic microbes but its hydroxyl metaboliteenhances its effect even against other group of bacteria(Pavicic et al)

Upon entry into an organism, metronidazole is reducedat 5-nitro position by electron transport proteinsproducing free radicals. These react with bacterial DNAcausing cell death. Hence it is primarily a bactericidalagent (Drisko et al).

Serum concentration of Metronidazole has shown toattain MIC levels for most periodontal pathogens (Britand Prohlod 1986) and it is found to eliminate

spirochetes from ANUG lesions.


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METRONIDAZOLE DENTAL GELELYZOL)

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


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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 theevaluation of metronidazole as an alternative to

SRP

(Pavia et al 2004)


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Doxycycline

Minocycline


Ofloxacin

Others


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CHLORHEXIDINE It is a topical antiseptic belonging to the family of

bisguanides. It is mainly active against gram +veorganisms

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 singleapplication (Soskolne et al 1998)


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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


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TECHNIQUEAfter 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 chipplacement, placement of multiple chips around a singletooth may result in discomfort

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

Instructions given to the patient is in lieu withtetracycline fibres


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Periocol-CG (Eucare)


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( )

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
http://dx.doi.org/10.4103/0976-237X.114848http://dx.doi.org/10.4103/0976-237X.114848http://dx.doi.org/10.4103/0976-237X.114848http://dx.doi.org/10.4103/0976-237X.114848


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doi: 10.4103/0976 237X.114848

PMCID: PMC3757875

Comparison of the efficacy of chlorhexidine varnish and chip in the treatment of

chronic periodontitisB. S. Jagadish Pai, Smitha Anitha Rajan, M. Srinivas, R. Padma, Girish Suragimath,Amit Walvekar, Saakshi Goel, andVinesh

KamathBackground:

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 3rdsite 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

30th

day and 90th

day from baseline when compared to SRP alone. The results though were notstatistically significant
http://www.ncbi.nlm.nih.gov/pubmed/?term=Jagadish%20Pai%20BS[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Rajan%20SA[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Srinivas%20M[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Padma%20R[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Suragimath%20G[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Walvekar%20A[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Walvekar%20A[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Goel%20S[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Kamath%20V[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Kamath%20V[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Kamath%20V[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Kamath%20V[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Kamath%20V[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Goel%20S[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Goel%20S[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Goel%20S[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Walvekar%20A[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Walvekar%20A[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Suragimath%20G[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Suragimath%20G[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Suragimath%20G[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Padma%20R[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Srinivas%20M[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Srinivas%20M[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Rajan%20SA[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Rajan%20SA[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Rajan%20SA[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Rajan%20SA[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Rajan%20SA[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Jagadish%20Pai%20BS[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Jagadish%20Pai%20BS[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Jagadish%20Pai%20BS[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Jagadish%20Pai%20BS[auth]


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Doxycycline

Minocycline


Ofloxacin

Others


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OFLOXACINOfloxacin belongs to quinolone family which

constitute a group of 1,8 naphthyridine derivativesand are synthetically produced drugs

They are considered to be bactericidal as theyinhibit 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 DNAreplication and continued protein synthesis results

in inhibition of cell division


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OFLOXACIN INSERTS PT-01)Okade and co-workers

PT-01 is a soluble insert, with both fast andsustained 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 atapproximately 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


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Initial investigations failed to any additional

microbiological effect in a split mouth design

(Kimura et al 1991)

Further investigations byYamagami et al (1992)

showed four weekly applications of the insert

resulted in significant resolution of periodontalinflammation and improvement in other clinical

parameters.


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COMPARISON OF DRUGS USED FOR LOCAL


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DELIVERY

FUTURE TRENDS


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FUTURE TRENDS

CLARITHROMYCIN GELA 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 PRODUCTSVarious 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.


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NANOPARTICLES, owing to their small size,


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, g ,

penetrate regions that may be inaccessible to other

delivery systems. These systems reduce the

frequency of administration and further provide auniform 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


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a) Dung et al used Antisense oligonucleotide- loadedchitosantripolyphosphate (TPP) nanoparticles and showed thesustained release of oligonucleotides which is suitable for the localtherapeutic application in periodontal diseases

b) Pinon et al conducted a preliminary in vivo study in dogs withinduced periodontal defects using Triclosan-loaded polymeric (PLGA,PLA and cellulose acetate phthalate) nanoparticles and suggestedthat triclosan- loaded nanoparticles penetrate through the junctionalepithelium.

c) Moulari et. al, investigated the in vitro bactericidal activity of theHarungana madagascariensis leaf extract (HLE) on the oralbacterial strains largely implicated in dental caries and gingivitisinfections. HLE-loaded PLGA nanoparticles were prepared using

interfacial polymer deposition following the solvent diffusion method.Incorporation of the HLE into a colloidal carrier improved itsantibacterial performance and diminution of the bactericidalconcentration was observed.


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Journal of PeriodontologyJanuary 2013, Vol. 84, No. 1, Pages 24-31 , DOI 10.1902/jop.2012.110721(doi:10.1902/jop.2012.110721)
http://www.joponline.org/loi/jophttp://www.joponline.org/loi/jophttp://www.joponline.org/loi/jop


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Efficacy of Subgingivally Delivered Simvastatin in theTreatment of Patients With Type 2 Diabetes and ChronicPeriodontitis: A Randomized Double-Masked Controlled

Clinical TrialA.R. Pradeep,*Nishanth S. Rao,*Pavan Bajaj,*and Minal Kumari**Department of Periodontics, Government Dental Collegeand Research Institute, Bangalore, India.

Background:Simvastatin(SMV) is a specific competitive inhibitor of 3-hydroxy-2-methyl-glutarylcoenzyme A reductase. Recently, it has been reported that statins promote bone formation. Thepresent study is designed to investigate the effectiveness of 1.2% SMV in an indigenouslyprepared, biodegradable, controlled-release gel as an adjunct to scaling and root planing (SRP) inthe 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% SMVand 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), andclinical attachment level (CAL). At baseline and after 6 and 9 months, radiologic assessment ofintrabony 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 ofbone 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 CALgain with significant IBD fill at sites treated with SRP plus locally deliveredSMV 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
http://dx.doi.org/10.7860/JCDR/2013/5793.3517http://dx.doi.org/10.7860/JCDR/2013/5793.3517http://dx.doi.org/10.7860/JCDR/2013/5793.3517http://dx.doi.org/10.7860/JCDR/2013/5793.3517


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PMCID: PMC3843431

Clinical Effects of Subgingivally Delivered Spirulina Gel in ChronicPeriodontitis Cases: A Placebo Controlled Clinical TrialJaideep Mahendra,1Little Mahendra,2Jananni Muthu,3Libby John,4and Georgios E. Romanos5

Aims and Objectives:The aim of this study was to assess the clinical effects ofSpirulina in-situ gel as an adjunct to Scaling And Root Planning (SRP) in the treatmentof chronic periodontitis subjects.

Material and Methods:64 sites were selected with probing pocket depth of 5mm andthey 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 decreasein mean probing pocket depth and gain in the clinical attachment level after 120 daysas compared to Group B SRP alone.

Conclusion:Locally delivered spirulina gel, along with scaling and rootplanning, has been shown to cause a beneficial impact. The efficacy of the productas a local drug delivery system in the non-surgical treatment of periodontitis withoutany side effects has been proved. Spirulina appears to be promising. It exerts stronganti-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
http://www.ncbi.nlm.nih.gov/pubmed/?term=Mahendra%20J[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Mahendra%20L[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Muthu%20J[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=John%20L[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Romanos%20GE[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Romanos%20GE[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=John%20L[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Muthu%20J[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Muthu%20J[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Muthu%20J[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Mahendra%20L[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Mahendra%20J[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Mahendra%20J[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Mahendra%20J[auth]http://dx.doi.org/10.4103/0972-124X.113069http://dx.doi.org/10.4103/0972-124X.113069http://dx.doi.org/10.4103/0972-124X.113069http://dx.doi.org/10.4103/0972-124X.113069


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Green tea extract as a local drug therapy on periodontitis patients with diabetes mellitus: A randomized

casecontrol study

Jayaprakash S. Gadagi, Vijay K. Chava,1and 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 atincorporation 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 vitrostudy, 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 vivostudy, 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 theplacement 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 actinomycetemcomitanswas

performed at baseline and fourth week.

Results:

The in vitrostudy showed 10.67% green tea release at 30 min; thereafter, a slow release was noted till 120

min. In vivostudy: Both groups showed significant reduction in GI scores at the test sites. Group 1 showedsignificant (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.

gingivalisin 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.
http://www.ncbi.nlm.nih.gov/pubmed/?term=Gadagi%20JS[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Chava%20VK[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Reddy%20VR[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Reddy%20VR[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Reddy%20VR[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Reddy%20VR[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Reddy%20VR[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Chava%20VK[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Gadagi%20JS[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Gadagi%20JS[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Gadagi%20JS[auth]http://www.ncbi.nlm.nih.gov/pubmed/?term=Gadagi%20JS[auth]


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Exposure to sub inhibitory concentrations of


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metronidazole or minocycline resulted in

development of resistance among

P.gingivalis,P.intermedia,

F.nucleatum and

P.anaerobiusWalker et al, Larsen et al

This suggests that repeated use of these agentscan result in increased levels of drug resistant

bacteria


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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 ofperiodontitis

(Tonetti 2000)

DISEASES THAT CAN BE TREATED WITH


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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.


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Thus, at present there is no concrete evidence

to use local delivery agents in the treatment ofaggressive 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
http://www.ncbi.nlm.nih.gov/pubmed/23320860http://www.ncbi.nlm.nih.gov/pubmed/23320860http://www.ncbi.nlm.nih.gov/pubmed/23320860http://www.ncbi.nlm.nih.gov/pubmed/23320860http://www.ncbi.nlm.nih.gov/pubmed/23320860http://www.ncbi.nlm.nih.gov/pubmed/23320860


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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

REMEM ER
http://www.ncbi.nlm.nih.gov/pubmed?term=Matesanz-P%C3%A9rez%20P[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Garc%C3%ADa-Gargallo%20M[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Figuero%20E[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Bascones-Mart%C3%ADnez%20A[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Sanz%20M[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Herrera%20D[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Herrera%20D[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Sanz%20M[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Sanz%20M[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Sanz%20M[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Bascones-Mart%C3%ADnez%20A[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Bascones-Mart%C3%ADnez%20A[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Bascones-Mart%C3%ADnez%20A[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Bascones-Mart%C3%ADnez%20A[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Bascones-Mart%C3%ADnez%20A[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Figuero%20E[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Figuero%20E[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Figuero%20E[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Garc%C3%ADa-Gargallo%20M[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Garc%C3%ADa-Gargallo%20M[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Garc%C3%ADa-Gargallo%20M[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Garc%C3%ADa-Gargallo%20M[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Garc%C3%ADa-Gargallo%20M[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Matesanz-P%C3%A9rez%20P[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Matesanz-P%C3%A9rez%20P[Author]&cauthor=true&cauthor_uid=23320860http://www.ncbi.nlm.nih.gov/pubmed?term=Matesanz-P%C3%A9rez%20P[Author]&cauthor=true&cauthor_uid=23320860


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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 tothis adjunctive treatment method may be refractory

or recurrent periodontitis

REMEMBER..


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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


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The number of problems encountered in delivering the drugsto the intended target site with the right dosage is a challenge

to the clinician since drugs often have limited solubility, sufferbreakdown before they reach their target tissues and mightcause 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 drugdelivery systems have high stability than conventional

delivery mechanisms

Therefore, the introduction of nanoparticle delivery system

has been tried & has gained popularity

CONCLUSION


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Various drug delivery and drug targeting systems arecurrently under development to obtain

Increased dissolution velocity

Increased saturation solubility

Improved bioadhesivity and

Versatility in surface modification

so that better and effective administration of desiredand newer drug can be done through the bestpossible system

Long term longitudinal studies to be done to know thedurability of these drugs on long term basis

REFERENCES


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1. Clinical periodontologycarranza

2. Jan Lindhe

3. Dental Clinics of North America January 2010 volume 54number 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 locallydelivered 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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THANK YOU

Local Drug Delivery by Heta

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