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Local Drug Delivery Systems

Dr.T.R.Aravindhan MDS Senior Lecturer Department Of Periodontics Sri Ramachandra Dental College

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 .

little or no effect on host tissues (Goodson 1985) Retentive after placement.Ideal requisites of locally administered agents Must deliver the drug to the base of pocket. ease of placement and cost effective biodegradable (Greenstein and Polson 1998) . Be there for sufficient period of time. Must have microbiologically effective concentrations in the pocket.

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

Controlled release devices ± designed to provide drug release that at least exceeds 1 day. or for at least 3 days following application (Kornman1993). Sustained release devices ± designed to provide drug delivery for less than 24 hours. b. Based on the duration of medicament release (Greenstein and Tonetti 2000): a. .II.

Based on physical form (Soskolne 1997): a. nonbiodegradable IV. Films/slabs eg chlorhexidine chip c.III. Injectable form eg minocycline . Based on degradation: a. Fibers eg tetracycline b. biodegradable b.

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 periodontitis Pharmacokine 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 .

alternative for patients predisposed to adverse reactions from systemic antibiotic administration. (Goodson 1989) .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. lower total drug dosage. with patient compliance. Reduced risk for drug resistant microbe development at nonoral body sites. (Rams and Slots) increased access to the site.

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. .

Non responding sites to conventional therapy in well motivated patients. as a monotherapy.Indications and Contraindications Indications: As an adjunct to root surface instrumentation in pockets of 5 mm or greater . to pregnant and lactating mothers (for tetracycline group of drugs). Contraindications: allergic to particular drug used. to be used with caution in patients with history of immune deficiency (to prevent the overgrowth of candida or other resistant organisms). Localized recurrent pockets in patients under supportive periodontal therapy. .

pain on insertion. burning sensation on insertion (with Chlorhexidine) development of abscesses interference with taste Tonetti (2000) . occurrence of candidiasis especially.Adverse effects Allergic reactions might produce resistant strains or overgrowth of intrinsically resistant organisms.

g.Drug Selection effective therapy matches the putative pathogen with an appropriate drug is advisable to do bacterial culture and sensitivity testing e. as they are broad spectrum antibiotics. . 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. tetracyclines often administered. However studies also showed patients previously treated with tetracycline responded not well and other antibiotics were beneficial (Magnusson 1989)..

. Tetracycline. Hence resistance to one indicates resistance to all the three. 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.Various Drugs Used as Controlled Released Systems 1. Doxycycline and Minocycline are commonly used with similar spectrum of activity.

when applied topically thereby enhancing attachment of fibroblasts to the tooth surface (Wikesjo et al 1986. Demineralizes dentin cementum and dentin. it also possess the following functions: 1. In addition to its antibacterial action. These drugs principally acts by inhibiting protein synthesis.are considered as bacteriostatic agents but may have a bactericidal effects in high concentrations (Walker 1996). 2. Ingman et al 1993). Inhibits most of mammalian collagenases (Golub et al 1984. Morrison et al 1992) .

detectable in crevicular fluid several weeks following application (Wikesjo et al 1986). after local delivery have been detected at 1-20µm within epithelial tissues (Ciancio et al 1992).Advantage of tetracycline as Controlled Released Systems: has high substantivity. 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 .

5 mm in diameter. The fiber is flexible. these fibers provide bactericidal concentration of tetracycline. 23 cm in length and 0.Tetracycline fibers (Actisite) are non-resorbable cylindrical drug delivery devices made of a biologically inert. At a concentration more than 150 times achieved by systemic tetracycline. 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. and can be folded on itself to nearly fill the pocket able to produce and maintain a concentration of 1. . plastic co-polymer loaded with 25% tetracycline HCL powder (Goodson et al 1983).

Resorbable fibers: Minabe (1989) described a device in which tetracycline is incorporated into cross-linked collagen matrix. . Monolithic fibers: prepared by melt extrusion technique. atelocollagen.5 mm fiber and they provide a controlled release system (Goodson et al 1985).Types of fibers Hollow fibers: cellulose acetate fibers are filled with tetracycline and they provide only sustained release system. 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. a mixture of 25% tetracycline HCl and 75% ethylene vinyl acetate was heated to 214 C and extruded as 0. wherein.

The fiber might be folded on itself The folding procedure might be repeated until all the pockets are nearly filled. Short lengths of fiber. . 2-3 inches are taken in a cotton forceps and placed at the opening of the pocket o be treated.Technique An individual or several teeth can be treated at a time.

Alternatively. Fibers should be in place for 7-14 days. tooth dried with the air syringe. They can be teased out of the pockets with a curette.Interproximal pockets should be packed from both the buccal and the lingual sides. and a drop of tissue adhesive applied at each interdental area as well as facially and lingually. . periodontal pack can be placed (Goodson et al 1985). After placement. the area is isolated with cotton rolls or gauze. Fiber removal (in case of non-resorbable fibers). is fairly simple.

. To rinse with chlorhexidine mouth rinse while the fibers are in place and for 1 week after their removal. To come for recall visit at 4-6 weeks.Instructions to be given to the patient not to brush or floss the treated areas until fibers are removed. Advised to return back to normal original oral hygiene procedure after 1 week or after fiber removal (in case of non-resorbable fibers).

3 and 6 months than scaling root planing alone. . The combination therapy showed significant clinical improvements including attachment levels at 1. Newman et al (1994) in longitudinal trial. The bacteria in the group treated with tetracycline fibers showed increased holes demonstrating bactericidal activity of tetracycline. 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. longitudinal trial evaluated tetracycline fiber Vs placebo fiber Vs scaling root planing and no treatment.Studies showing the efficacy of Tetracycline fibers Goodson et al (1991). scaling root planing Vs scaling root planing and tetracycline fibers in maintenance patients.

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).

chosen : mechanism of action. Doxycycline polymer (Atridox) A biodegradable formulation containing 10% by weight doxycycline. McCulloch et al 1990). 33% by weight poly (DL-Lactide) and 57% by weight N-methyl 2pyrrolidone was developed. .2. It is a liquid biodegradable system that hardens when placed in periodontal pocket. activity against putative periodontal pathogens and effective in the management of human diseases (Golub et al 1984.

the polymer slightly protrudes from the pocket orifice. 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. The cannula has a diameter of a periodontal probe. . which is bent is used in a similar diagnostic and tactile manner. it is packed into the pocket using the underside of the moistened curet or other blunt-ended instrument.Technique Liquid delivery system containing 10% doxycycline hyclate is contained within a syringe that has a blunt ended 23 gauge cannula attached. Periodontal dressing or adhesive is used as an aid in retention of the system. Immediately after administration. Instructions given to the patient is in lieu with tetracycline fibers.

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.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. .

thereby precluding the use of doxycycline polymer. repeated applications annually had no clinical or microbiologic effects beyond those observed with mechanical debridement alone in maintenance patients. Bogren et al (2008) : short-term effects on clinical parameters were found with the adjunctive use of doxycycline. .Jorgensen et al (2004) : no significant additional reduction in the subgingival pathogenic microbiota compared to thorough scaling root planing alone.

However. . 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. disruption of biofilm and removal of calculus is required prior to application of this drug.Thus.

I hour after single topical administration of 0. .Minocycline (Dentomycine and Periocline) 3 modes of local application are available: film. The concentration of minocycline in the pocket was 1300 µg/ml.05 ml ointment and decreased to 90 µg/ml after 7 hours (Satomi et al). microspheres or ointment. It is a bacteriostatic antibiotic.

Film ethylcellulose containing 30% of minocycline cast from ethanol. chloroform or chloroform with polyethylene glycol were tested ass sustained release devices (Elkayam et al). Microspheres: Minocycline micro-encapsulated in a resorbable poly (glycolide-lactide) slow release polymer (Braswell et al). The volume of microspheres in each syringe is 4 mg which is equivalent to 1 mg of minocycline base. 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. . this can be administered by means of disposable plastic syringe.

3 applications at 2 weekly intervals were effective. supplied in a disposable polypropylene applicator and each applicator contains the equivalent of 10 mg minocycline in 0. 1 applications per week for 4 weeks. 60 mg triacetine and glycerine 0. Repeated applications of 2% minocycline.5 g. 10 mg eudragit RS. 2 applications at intervals of 1 or 2 weeks. .5 g ointment.Ointment: It is a light yellow colored ointment base of 20 mg hydroxyethyl cellulose.

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. .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.

but the treatment may have to be repeated. . Renvert et al (2008) use of a local antibiotic as an adjunct to the mechanical treatment of periimplantitis 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.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.

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

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

as indicated by peak plasma concentration observed 2-8 hours following administration (Stolze et al 1992). or absorbed through the mucosa. A substantial amount of this drug can be swallowed. The gel is subgingivally placed with a syringe and a blunt cannula. .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. Decay of the drug concentration in crevicular fluid follows an exponential pattern which is compatible with sustained drug delivery.

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. . Ainamo et al (1992) Metronidazole as a mono therapy Vs scaling and planing and monotherapy is equally effective as scaling and planing. All the groups produced similar clinical effects with no evidence of any adverse effects.

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. .

. 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).Thus the effectiveness of metronidazole as an adjunct to SRP in the treatment of chronic adult periodontitis.

It is mainly active against gram positive group of organisms.Chlorhexidine It is a topical antiseptic belonging to the family of bisguanides. It has been detected in excess of 125 µg/ml in crevicular fluid for 1 week following a single application (Soskolne et al 1998). . It is bacteriostatic at lower and bactericidal at higher concentrations.

5 mm wide. and 1 mm thick pliable strip loaded with 2. Each chip is 5 mm long. .Chlorhexidine chip (Periochip) It is a bioabsorbable device comprising 34% Chlorhexidine in a cross linked gelatin matrix.5 mg of Chlorhexidine.

. The chip degrades in a period of 7-10 days and requires no retentive system. As burning sensation is reported after the chip placement.Technique After scaling and root planing. the chip is grasped in a cotton forceps and gently inserted into the pocket. Instructions given to the patient is in lieu with tetracycline fibers. It is advisable to dry the area before placing the chip. placement of multiple chips around a single tooth may result in discomfort.

planing when compared to scaling .planing is beneficial in improving periodontal parameters in patients under supportive periodontal therapy.planing alone.planing alone and found there is improvement in attachment level in pockets even more than 7mm in the combination group.planing Vs scaling . . this can be combined with mechanical debridement to achieve effective treatment outcomes. like other drugs.Studies showing the efficacy of Chlorhexidine Soskolne et al (1997) chlorhexidine and scaling . Jeffcoat et al (1997) in a 9 month study. clinical improvement in periodontal parameters when chlorhexidine chip was combined with scaling . Kasaj et al (2007) showed chlorhexidine chip application following scaling . Thus.

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.Ofloxacin Ofloxacin belongs to quinolone family which constitute a group of 1. 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. 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). 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. with both fast and sustained release parts containing 10% w/w ofloxacin.

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. .

it is predominantly a bacteriostatic drug and interfere with bacterial protein synthesis by binding to 50s ribosomal unit. derived from macrolides (Walker 1996). penetrate both healthy and diseased periodontal sites and to maintain chemotherapeutic levels in excess of the MICs of majority of periodontopathogens.g. and P.Azithromycin This belongs to azalide group of antibiotics. . good in vitro activity against all serotypes of A. broad spectrum activity against a number of bacteria including gram negative anaerobes and provides excellent and prolonged drug concentration in tissues and serum.a.

(Pradeep et al 2008).5% concentration in an indigenously prepared bioabsorbable controlledrelease gel as an adjunct to non-surgical mechanical therapy in the treatment of chronic periodontitis was evaluated by comparing with scaling and planing alone. the adjunctive use of 0. .azithromycin at 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. Although both treatment strategies seemed to benefit the patients.

Comparison of drugs used for local delivery Drug Tetracycline (FDA approved) Metronidazole Chlorhexidine (FDA approved ) Minocycline gel Doxycycline (FDA approved ) Resorbable time (in days) No 1 8 Type of release Controlled Sustained Controlled 1 27 Sustained 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 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 Systemic delivery 1. Less concentration in the pocket 2. More adverse effects 3. Patient compliance is relied on 4. 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 time 9. Do not have

especially in a systemic way. Therefore. Their results showed no difference in clinical results between the groups. . in the treatment of chronic adult periodontitis. the use of antibiotics on a routine basis. the local application of minocycline.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%. can no longer be advocated. Bernimoulin et al (1996) compared local application of tetracycline fibers with systemic administration of amoxicillinclavulanate potassium. and the systemic use of metronidazole or doxycycline seem to result in a prolonged supplementary effect when compared to scaling and root planing.also supported by Noyan et al (1997) and Drisko et al (1993).

. The local alone treatment seemed more effective than systemic treatment on pocket reduction. The systemic group showed lower pocket reduction while no significant difference was found between local and scaling-planing group. but no significant difference was found between them when combined with the scaling-planing.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. Thus local doxy may be more preferable than systemic doxy as an adjunct to mechanical treatment.

Thus. localized nonresponding 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). it can be concluded local delivery systems are logical adjuncts for the treatment of a few.

Diseases that can be treated with local drug delivery systems All drugs were used to treat patients with chronic periodontitis. despite in vitro susceptibility of that organism. Mombelli et al (1997) reported tetracycline fibers were able to suppress. Only tetracycline fibers and metronidazole were used to treat aggressive periodontitis.a. but not eliminate A. With regard to juvenile periodontitis. also suggested that these fibers were not efficient in suppressing A. On the other hand.a or P. 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.g. . as they might harbor increased levels of these above said organisms. tetracycline fibers were not effective for treatment in a study by (Mandell 1986) .

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

Both groups showed clinical improvements but there was no difference in the attachment level between the groups. Minabe et al (1991) treated grade 2 furcation involved molars with atelocollagen tetracycline delivery system either with or without scaling and root planing. .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. 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. as per today knowledge. local drug delivery systems cannot replace surgery or can it be used to treat any defect. Thus. .

Local delivery may be an adjunct to conventional therapy.POINTS TO REMEMBER There is no single universal drug that would be effective in all situations. The sites most likely to be responsive to this adjunctive treatment method may be refractory or recurrent periodontitis. 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.

regarding the ability of local delivery to help suppress future disease progression. In conjunction with conventional treatment. There are only limited data to indicate that local drug delivery induces bacterial resistance to antimicrobial agents.At present. there are insufficient data to indicate that one local drug delivery service is clearly superior to all the other systems. . There are only preliminary available. Long term studies are needed to address this important issue. systematically administered drugs appear to be as effective as local drug delivery.

Cigarette smoking has a negative influence on outcome of local drug therapy (Kinane et al 1999).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. . Long term longitudinal studies to be done to know the durability of these drugs on long term basis.

However.Conclusion The current data suggest that local delivery of antimicrobials into the periodontal pocket can improve periodontal health. 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) . they do not provide a superior result to scaling and root planing.