Local Drug Delivery Systems

Dr.T.R.Aravindhan MDSSenior Lecturer

Department Of PeriodonticsSri Ramachandra Dental College

INTRODUCTION• Periodontal diseases are poly

microbial infections• removal of this biofilm by

mechanical instrumentation is essential.

• also prudent use of chemotherapeutic agents becomes mandatory to produce ideal results.

Limitations of mechanical debridement

• Unfavorable anatomy • Intra oral microbial translocation• Tissue invasive organisms • Bacterial invasion into dentinal tubules

Quirynen et al (2002)

Pocket Dynamics

• Invasive bacteria • Effect of biofilm• Resistant organisms• Drug binding• Periodontal Clearance

Slots and Winkelhoff

1993

Ideal requisites of locally administered agents • Must deliver the drug to the base of pocket.

• Must have microbiologically effective concentrations in the pocket.

• Be there for sufficient period of time.• little or no effect on host tissues

(Goodson 1985)

• Retentive after placement.• ease of placement and cost effective• biodegradable

(Greenstein and Polson 1998)

Classification

I. Based on application (Rams and slots): i. Personally applied: a. Nonsustained subgingival delivery – home oral irrigation b. Sustained subgingival drug delivery – none developed to date ii. Professionally applied in dental office: a. Nonsustained subgingival delivery – pocket irrigation b. Sustained subgingival drug delivery – controlled release device

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 1 day, or for at least 3 days following application (Kornman1993).

III. Based on degradation: a. biodegradable b. nonbiodegradable

IV. Based on physical form (Soskolne 1997):

a. Fibers – eg tetracycline b. Films/slabs – eg chlorhexidine chip c. Injectable form – eg minocycline

Controlled Release Local delivery systems

• Reservoirs without rate controlling systems

• Reservoirs with rate controlling systems

(Kornman1993)

Comparison of drug delivery systems for the management of periodontitisPharmacokine

tic variable Mouth

rinse Subgingival

irrigation

Systemic delivery

Controlled delivery

Site delivery

Poor

Good

Good

Good

Concentration

Good

Good

Fair

Good

Duration Poor

Poor Fair Good

Advantages and disadvantages of Controlled drug delivery systems

Advantages:

• can attain 100 fold higher concentrations • can employ agents that are not suitable for systemic

administration, • with patient compliance.• alternative for patients predisposed to adverse reactions

from systemic antibiotic administration.• Reduced risk for drug resistant microbe development at

nonoral body sites.

(Rams and Slots)• increased access to the site.• lower total drug dosage. (Goodson 1989)

Disadvantages:

• Difficulty in placing therapeutic concentrations into deeper part of periodontal pockets and furcation lesions.

• Time consuming and labor intensive • Do not have effect on bacteria residing

on extra pocket oral niches • Cannot be used for aggressive

periodontal diseases.

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.• as a monotherapy. to 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• effective therapy matches the putative

pathogen with an appropriate drug • is advisable to do bacterial culture and

sensitivity testing 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 (Magnusson 1989).

• arbitrary selection of antibiotics for local delivery has the same limitations as empirical selection for systemic administration.

• no single drug is the universal drug of choice.

Various Drugs Used as Controlled Released Systems1. Tetracycline

• are broad spectrum antibiotics with activity against both gram positive and gram negative 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.

• are considered as 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 possess the following functions:

1. Inhibits most of mammalian collagenases (Golub et al 1984; Ingman et al 1993). 2. Demineralizes dentin cementum and

dentin, when applied topically thereby enhancing attachment of fibroblasts to the tooth surface

(Wikesjo et al 1986; Morrison et al 1992)

• Advantage of tetracycline as Controlled Released Systems:

• has high substantivity, after local delivery have been detected at 1-20µm 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.

Serum and GCF concentration of commonly used antibiotics

Drug Serum concentration

(µg/ml)GCF concentration

(µg/ml)

Tetracycline 3-4 5-12

Amoxicillin 8 3-4

Metronidazole 6-12 8-10

Doxycycline 2-3 2-8

Tetracycline fibers (Actisite)

• 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 fiber is flexible, and can be folded on itself to nearly fill the pocket

• able to produce and maintain a concentration of 1, 300µg/ml for a period of 7 days (Tonetti et

al 1990) with mean concentrations of 43µg/ml in the superficial portions of the pocket wall.

• At a concentration more than 150 times achieved by systemic tetracycline, these fibers provide bactericidal concentration of tetracycline.

Types of fibers

• Hollow fibers: cellulose acetate fibers are filled with tetracycline and they provide only sustained release system.

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

• Resorbable fibers: Minabe (1989) described a device in which tetracycline is incorporated into cross-linked collagen matrix, atelocollagen, capable of delivering tetracycline in the crevicular fluid at therapeutic levels for upto 10 days after insertion and drug levels ranged from 17 to 180µg/ml.

Technique• An individual or several teeth can

be treated at a time. • Short lengths of fiber, 2-3 inches

are taken in a cotton forceps and placed at the opening of the pocket o be treated.

• The fiber might be 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).

• Fibers should be in place for 7-14 days. • Fiber removal (in case of non-resorbable

fibers), 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 fibers are removed.

• To rinse with chlorhexidine mouth rinse while the fibers 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 fiber removal (in case of non-resorbable fibers).

• To come for recall visit at 4-6 weeks.

Studies showing the efficacy of

Tetracycline fibers• Goodson et al (1991), longitudinal trial evaluated tetracycline fiber Vs placebo fiber Vs scaling root planing and no treatment.

significant improvement in all the periodontal parameters in tetracycline

• Morrison et al (1992) : scaling root planing alone Vs scaling root planing and tetracycline fibers Vs tetracycline fibers on the bacteria attached to the tooth surface. The bacteria in the group treated with tetracycline fibers showed increased holes demonstrating bactericidal activity of tetracycline.

• Newman et al (1994) in longitudinal trial, scaling root planing Vs scaling root planing and

tetracycline fibers in maintenance patients. The combination therapy showed significant clinical

improvements including attachment levels at 1, 3 and 6 months than scaling root planing alone.

• Michalowicz et al (1995) showed that scaling and root planing in conjunction with fibers for 10 days can significantly reduce disease recurrence 3-12 months following treatment.

• Freisen et al (2002) showed local delivery of tetracycline is superior to root planing alone in reducing probing depth and bleeding on probing.

• 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).

2. 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.

• chosen : mechanism of action, activity against putative periodontal pathogens and effective in the management of human 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, which is bent is used in a similar diagnostic and tactile manner.

• 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 curet 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 fibers.

Studies showing the efficacy of Doxycycline

• Polson et al (1997) in a 9 month trial. Doxycycline Vs sanguinarine Vs vehicle alone

showed doxycycline was superior to sanguinarine and vehicle with respect to improvement in all periodontal parameters inclusive of attachment gain and exhibited a safety profile.

• Garrett et al (1999) in 2 large, randomized controlled clinical trials

Doxycycline Vs scaling and root planing indicated there was no difference between the therapies with regard to probing depth reduction or gain in attachment.

• Jorgensen et al (2004) : no significant additional reduction in the subgingival pathogenic microbiota compared to thorough scaling root planing alone, thereby precluding the use of doxycycline polymer.

• Bogren et al (2008) : short-term effects on clinical parameters were found with the adjunctive use of doxycycline, repeated applications annually had no clinical or microbiologic effects beyond those observed with mechanical debridement alone in maintenance patients.

• Thus, at present there are no conclusive data available regarding the ability of doxycycline polymer to enhance periodontal health when used in conjunction with root planing. However, disruption of biofilm and removal of calculus is required prior to application of this drug.

Minocycline (Dentomycine and Periocline)• 3 modes of local application are

available: film, microspheres or ointment.

• It is a bacteriostatic antibiotic. The concentration of minocycline in the pocket was 1300 µg/ml, I hour after single topical administration of 0.05 ml ointment and decreased to 90 µg/ml after 7 hours (Satomi et al).

• Film• ethylcellulose containing 30% of minocycline

cast from ethanol, chloroform or chloroform with polyethylene glycol were tested ass 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 for 14 days.

• Microspheres:• Minocycline micro-encapsulated in a resorbable

poly (glycolide-lactide) slow release polymer (Braswell et al), this 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.

• 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 applications per week for 4 weeks, 2 applications at intervals of 1 or 2 weeks, 3 applications at 2 weekly intervals were effective.

Studies showing the efficacy of Minocycline:• van Steenberghe et al (1993)

Minocycline ointment or vehicle (4 administration) with single session of scaling and planing showed combination treatment is effective than the vehicle control. This was also supported by Murayama et al (1988).

• Timmerman et al (1996) minocycline and debridement is not

superior to vehicle and debridement in pockets more than 7 mm deep.

• Paquette (2002) no increased incidence of adverse events or tetracycline resistance was observed with minocycline-microsphere treatment, also indicate that minocycline microspheres plus scaling root planing are safe and more effective than scaling root planing alone in reducing the signs of chronic periodontitis.

• Renvert et al (2008) use of a local antibiotic as an adjunct to the mechanical treatment of peri-implantitis lesions demonstrated improvements in probing depths that were significantly different from controls and were sustained for 6 months. Thus adjunctive use of minocycline microspheres is beneficial in the treatment of peri-implant lesions, but the treatment may have to be repeated.

• Thus, minocycline can be used as a adjunct to mechanical debridement with improved effectiveness for treatment of chronic periodontitis Vanderkerckhove et al.

Metronidazole• a 5-nitroimidazole compound specifically targets

anaerobic microbes but has essentially no activity against aerobic or microaerophilic bacteria 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 The reduction of parent molecule produces 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)• is a bioabsosbable delivery device containing

25% Metronidazole benzoate in a matrix consisting of a mixture of glyceryl mono-oleate and sesame oil. The gel is subgingivally placed with a syringe and a blunt cannula. Decay of the drug concentration in crevicular fluid follows an exponential pattern which is compatible with sustained drug delivery.

• A substantial amount of this drug can be swallowed, or absorbed through the mucosa, as indicated by peak plasma concentration observed 2-8 hours following administration (Stolze et al 1992).

Studies showing the efficacy of Metronidazole• Klinge et al (1992) metronidazole gel

administered once in a week for 2 weeks in different concentrations Vs scaling and planing alone. All the groups produced similar clinical effects with no evidence of any adverse effects.

• Ainamo et al (1992) Metronidazole as a mono therapy Vs scaling and planing and monotherapy is equally effective as scaling and planing.

• Stetzel and Flores-de-Jacoby (1996) showed that Metronidazole gel either alone or in combination with mechanical debridement produced comparable results with mechanical debridement alone.

• Noyan et al (1997) compared systemic and local metronidazole administration as an adjunct to mechanical debridement and found locally delivered metronidazole is much more effective than systemically administered metronidazole when used in conjunction with mechanical debridement.

• Thus the effectiveness of metronidazole 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).

Chlorhexidine

• It is a topical antiseptic belonging to the family of bisguanides. It is mainly active against gram positive group of organisms.

• It is bacteriostatic at lower and bactericidal at higher concentrations.

• It has been detected in excess of 125 µg/ml in crevicular fluid for 1 week following a single application (Soskolne et al 1998).

Chlorhexidine chip (Periochip)

• It is a bioabsorbable device comprising 34% Chlorhexidine in a cross linked gelatin matrix. Each chip is 5 mm long, 5 mm wide, and 1 mm thick pliable strip loaded with 2.5 mg of Chlorhexidine.

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 fibers.

Studies showing the efficacy of Chlorhexidine• Soskolne et al (1997) chlorhexidine and scaling - planing

Vs scaling - planing alone and found there is improvement in attachment level in pockets even more than 7mm in the combination group.

• Jeffcoat et al (1997) in a 9 month study, clinical improvement in periodontal parameters when chlorhexidine chip was combined with scaling - planing when compared to scaling - planing alone.

• Kasaj et al (2007) showed chlorhexidine chip application following scaling - planing is beneficial in improving periodontal parameters in patients under supportive periodontal therapy.

• Thus, like other drugs, this can be combined with mechanical debridement to achieve effective treatment outcomes.

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)

• PT-01 is a soluble insert, with both fast and sustained release parts containing 10% w/w 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 12µg/ml and stabilizing at approximately 2µg/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 compared to controls.

Azithromycin

• This belongs to azalide group of antibiotics, derived from macrolides (Walker 1996).

• broad spectrum activity against a number of bacteria including gram negative anaerobes and provides excellent and prolonged drug concentration in tissues and serum.

• good in vitro activity against all serotypes of A.a, and P.g. it is predominantly a bacteriostatic drug and interfere with bacterial protein synthesis by binding to 50s ribosomal unit.

• penetrate both healthy and diseased periodontal sites and to maintain chemotherapeutic levels in excess of the MICs of majority of periodontopathogens.

• azithromycin at 0.5% concentration in an indigenously prepared bioabsorbable controlled-release gel as an adjunct to non-surgical mechanical therapy in the treatment of chronic periodontitis was evaluated by comparing with scaling and planing alone. Although both treatment strategies seemed to benefit the patients, the adjunctive use of 0.5% azithromycin as a controlled drug-delivery system enhanced the clinical and microbiologic results and the mean concentration of azithromycin at all observed periods (baseline to 28 days) is more than >2 µg/ml which has a potent antibacterial activity. (Pradeep et al 2008).

Comparison of drugs used for local delivery Drug Resorbable time

(in days)Type of release

Tetracycline(FDA approved) No Controlled

Metronidazole 1 Sustained

Chlorhexidine(FDA approved )

8 Controlled

Minocycline gel 1 Sustained

Doxycycline(FDA approved )

27 Controlled

• 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.

Antibiotic resistance associated with local drug delivery systems• Local drug delivery provides a high drug concentration at a

specific site, thereby reducing a potential due to ineffective drug dosing. However, 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.

• Goodson and Tanner noted that an initial increase in resistant organisms was not detectable after 6 months after the administration of tetracycline. Borden et al, Preus et al and Pedrazolli et al gave the same opinion with the use of doxy, minocycline and metronidazole respectively.

• But studies by Walker et al, Larsen et al indicated that exposure to sub inhibitory concentrations of metronidazole or minocycline resulted in development of resistance among P.gingivalis, P.intermedia, F.nucleatum and P.anaerobius.

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

Comparison between local and systemic drug delivery systems

Local Drug Delivery Systemic delivery

1. High concentration in the pocket 2. Minimal side effects 3. Less reliance on patient compliance 4. Avoids exposure of drug to non oral sites 5. Comparatively less penetration achieved 6. Potential reservoirs not treated

7. Tissues invasive organisms not always affected

8. Takes more time 9. Have a learning curve

1. Less concentration in the pocket2. More adverse effects3. Patient compliance is relied on4. Whole body is exposed to the drug

5. Delivery to base of the pocket achieved

6. Treat potential reservoirs of bacterial re infection

7. Affect tissue invasive organisms

8. Takes less time9. Do not have

• Bollen and Quirynen (1996) compared chlorhexidine 2% irrigation or local or systemic application of tetracycline or metronidazole Vs single course of scaling and root planing in patients with chronic adult periodontitis and showed only the irrigation with chlorhexidine 2%, the local application of minocycline, and the systemic use of metronidazole or doxycycline seem to result in a prolonged supplementary effect when compared to scaling and root planing. Therefore, the use of antibiotics on a routine basis, especially in a systemic way, in the treatment of chronic adult periodontitis, can no longer be advocated.

• Bernimoulin et al (1996) compared local application of tetracycline fibers with systemic administration of amoxicillin-clavulanate potassium. Their results showed no difference in clinical results between the groups,also supported by Noyan et al (1997) and Drisko et al (1993).

• Paquette et al (1994) compared metronidazole gel with systemic metronidazole and reported local delivery seem to be more efficacious than systemic therapy.

• Akalin et al (2004) evaluated the clinical efficacy of systemic and local doxycycline as an adjunct to scaling root planing with scaling root planing alone and found no significant difference between the systemic doxy and scaling root planing and the local doxy and scaling root planing treatments. The systemic group showed lower pocket reduction while no significant difference was found between local and scaling-planing group. The local alone treatment seemed more effective than systemic treatment on pocket reduction, but no significant difference was found between them when combined with the scaling-planing. Thus local doxy may be more preferable than systemic doxy as an adjunct to mechanical treatment.

• 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 fibers and metronidazole were used to treat aggressive periodontitis.

• With regard to juvenile periodontitis, tetracycline fibers were not effective for treatment in a study by (Mandell 1986) , also suggested that these fibers were not efficient in suppressing A.a, despite in vitro susceptibility of that organism. On the other hand, Mombelli et al (1997) reported tetracycline fibers were able to suppress, but not eliminate A.a or P.g.

• Riep et al (1996) reported local delivery of metronidazole too is not effective at suppressing A.a levels.

• These findings need to be considered when treating patients with these aggressive forms of disease, as they might harbor increased levels of these above said organisms.

• Thus, at present there is no concrete evidence to use local delivery agents in the treatment of aggressive periodontal diseases.

Defects that can be treated with local drug delivery systems• It is not proven well whether the adjuvant use of

systemic/local antibiotics might reduce the need for surgery or can these agents be used to treat osseous defects.

• Minabe et al (1991) treated grade 2 furcation involved molars with atelocollagen tetracycline delivery system either with or without scaling and root planing. Both groups showed clinical improvements but there was no difference in the attachment level between the groups.

• Kurtis et al (2002) evaluated the effect of polylactide/polyglycolide membranes loaded with metronidazole on periodontal regeneration following guided tissue regeneration in dogs and found no significant differences between metronidazole loaded and unloaded groups.

• Loesche et al (1996) addressed the issue of using adjuvant use of systemic/local antibiotics to mechanical instrumentation and indicated that that scaling and root planing with or without antibiotic usage may lead to a decrease in the perceived need for surgery.

• Thus, as per today knowledge, local drug delivery systems cannot replace surgery or can it be used to treat any defect.

POINTS TO 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 drug delivery systems usually do not provide a benefit beyond what is achievable with conventional scaling and root planing.

• 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.

• At present, there are insufficient data to indicate that one local drug delivery service is clearly superior to all the other systems.

• In conjunction with conventional treatment, systematically administered drugs appear to be as effective as local drug delivery.

• There are only preliminary available, regarding the ability of local delivery to help suppress future disease progression.

• There are only limited data to indicate that local drug delivery induces bacterial resistance to antimicrobial agents. Long term studies are needed to address this important issue.

• 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.

• Long term longitudinal studies to be done to know the durability of these drugs on long term basis.

• 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 current data suggest that local

delivery of antimicrobials into the periodontal pocket can improve periodontal health. However, they do not provide a superior result to scaling and root planing.

• In conjunction with scaling and root planing, the adjunctive use of local drug delivery devices may enhance the results in sites which do not respond to conventional therapy (Stanford 2001)