Basic to recent advances in local drug delivery also covering the effects of GCF flow on local drugs as well as use of local drugs used in periimplantitis.

1. 1

2. LOCAL DRUG DELIVERY
Presented by:
Ganesh Nair
Guided by:
Dr. Anita Panchal
Dr. Bhaumik Nanavati
Dr. Rahul Shah
Dr. Riddhi Gandhi
2

3. INDEX:
• Introduction
• Periodontal pharmacokinetics
• Factors Affecting Local Delivery of Agents in Periodontal
Pockets
• History and Development of periodontal local delivery devices
• Comparison of systemic vs local drug delivery
• Classification of LDD
• Antimicrobial effects of local delivery devices
• Efficacy of local delivery devices
• Clinical indications for treatment of periodontitis with
adjunctive local delivery devices
3

4. • Local conditions
• Special patient groups
• LDD in treatment of peri-
implantitis
• Antimicrobial agents used for
LDD:
▫ Tetracyclines
▫ Collagenase inhibitors
▫ Penicillins
▫ Clindamycin
▫ Azythromycin
▫ Metronidazole
▫ Chlorhexidine
▫ Ofloxacin
▫ Povidone iodine
• Other Agents Tried As LDD
• Conclusion.
4

5. Introduction:
• Treatment of periodontitis is routinely based on oral hygiene,
root debridement, and risk factor modification.
• Localized therapy has received significant attention because of
the site‐specific pattern of destruction of periodontal
infections and the potential side effects of systemic
antimicrobials and anti‐inflammatory agents.
5

6. • There are three basic routes to localized adjunctive
pharmacologic periodontal therapy:
1. mouth rinses (toothpaste or varnishes),
2. subgingival irrigation, and periodontal
3. application of local delivery systems.
6

7. Drawback of rinses:
• Rinses are useful for supragingival biofilm control,
modulation of gingival inflammation, and potentially for
recolonization of the subgingival environment following
periodontal treatment.
• Their major limitation, in the context of pharmacologic
therapy of periodontitis, is that they do not gain access to the
subgingival environment and therefore do not reach the
desired site of action (Pitcher et al. 1980).
7

8. Drawback of irrigation solution:
• Irrigation solutions placed directly into periodontal pockets initially
reach effective concentrations in the area, but the flow of the
gingival crevicular fluid (GCF) – which is replaced about 40 times
per hour – leads to rapid clearance of subgingivally placed drugs.
• Clearance of a medication locally placed in a periodontal pocket
follows exponential kinetics and it has been calculated that the
concentration of a highly concentrated irrigating solution of a
nonsubstantive (non‐binding) drug becomes ineffective about 15
minutes following application.
8

9. • Goodson – a pharmacologist who in the early 1970s pioneered
the field of local delivery to treat periodontitis pointed out
that successful pharmacologic control of the periodontal
microflora requires:
(1) delivery of an intrinsically efficacious drug to the site of
action (periodontal pocket and surrounding tissues);
(2) a concentration of the drug higher than the minimum
efficacious concentration; and
(3) maintenance of this concentration long enough for the effect
to occur.
9

10. Periodontal pharmacokinetics:
• Pocket volume and clearance:
• Clearance of a drug placed into a periodontal pocket follows
the exponential function:
• where C(t) is the concentration of the drug as a function of
time (t), C(0)is the initial concentration obtained in the GCF,
F is the GCF flow rate, and V is the resting fluid volume of the
pocket.
10

11. • Using an estimated periodontal pocket volume of 0.5 μL (Binder et al.
1987) and a GCF flow rate of 20 μL/h (Goodson et al. 1989), the
half‐time (the time that it takes to reach half of the initial concentration)
for a non‐substantive medication placed in the periodontal pocket will
be 0.017 hours (or about 1 minute).
• In the case of a substantive compound, the exponential function can be
rewritten by introducing a multiplicative constant K into the
denominator of the exponential term to account for binding of the drug
to the root surface (and/or periodontal pocket wall):
• where K is the affinity constant, which is experimentally estimated from
the determined clearance half‐time.
11

12. • This equation can be conveniently rearranged to estimate the
effect of the various parameters on the duration of the desired
therapeutic effect:
• where C(MIC) is the minimum inhibitory concentration
(MIC) and t(MIC)is the time taken to reach the MIC or the
expected time of antibacterial action.
12

13. • From this relation, it is apparent that the time over which a
therapeutic effect is observed ( t (MIC) ) will be longer when
the:
1. Volume of the pocket is large
2. GCF flow rate is low
3. Affinity constant for the drug is higher, that is a highly
substantive drugs is used
4. Initial concentration is very high, that is the drug has good
solubility in the applied vehicle
5. MIC is low, that is a very potent agent is used.
13

14. Factors Affecting Local Delivery of
Agents in Periodontal Pockets:
• Site of Action
• Targets for these agents are bacteria residing in periodontal
pocket and those in junctional epithelium, connective tissue,
cementum and dentine.
• Concentration
• Drug should have a dose higher than Minimal Inhibitory
Concentration (MIC). It is the in vitro concentration of drug
that inhibits or kills 90% of target organisms in culture.
14

15. • Time
• Once a drug reaches the site of action in an effective
concentration, it must remain at the site enough for its
pharmacological effect to occur. GCF clearance is very high.
Drug concentration will be affected by this.
• Mode of Delivery
• Fibers, gel, microspheres and chip.
15

16. History and Development of
periodontal local delivery devices:
• Goodson designed a first generation of local drug delivery
devices for application into periodontal pockets.
• The concept was to constantly replenish the free drug in the
periodontal pocket that is cleared by the GCF flow with the
release of drug from a drug reservoir placed into the
periodontal pocket (Goodson et al. 1979).
16

17. • These devices consisted of permeable hollow cellulose acetate
fibers (with an internal thickness of 200 μm) filled with a 20%
tetracycline– HCl solution. The fiber was tied around the
crevice of the pocket, pressed into the subgingival
environment, and removed after 24 hours.
• Better release profiles were obtained with a second generation
of devices characterized by a monolithic design (drug crystals
interspersed within an inert matrix) such as acrylic strips or
extruded ethylene vinyl acetate fibers (Addy et al. 1982;
Goodson et al. 1983).
17

18. • In particular, following placement of 0.5‐mm diameter 25%
tetracycline fibers, GCF concentrations in the order of 500–
1500 μg/mL were reported (Tonetti et al. 1989).
• Parallel efforts with bioresorbable matrices focused on
chlorhexidine in cellulose acetate (Soskolne et al. 1983) and
on release platforms made of hydroxypropylcellulose
(Noguchi et al. 1984) or collagen matrices (Minabe et al.
1989).
18

19. COMPARISON OF SYSTEMIC Vs LOCAL
DRUG DELIVERY
SYSTEMIC LOCAL
Route of administration Oral or parenteral Site specific
Pain, discomfort Not painful nil
Drug dosage Higher drug dosage (milli-grams) Lower dosage (micro-grams)
Peak levels Few hours in plasma
Pharmacokinetics Distribution in various body
compartments where antimicrobial effect
may not be required
Minimal distribution to different body
compartments at delivered sites
Frequency Once in 6-12 hrs Usually once a week
Superinfection Present Limited
Microbial resistance Present Limited
Patient compliance Required for better efficacy Patient delivered-required
Professional delivery-not required
Time required Less time Loner time if many sites are involved
Side effects More Limited
Effects on connective tissue associated
plaque
Effective Limited
19

20. Classification of LDD:
• LANGER AND PEPPAS (1988): Classified controlled drug release
polymeric system based on their mechanism of action.
I. Diffusion controlled systems
A. Reservoirs (membrane devices)
B. Matrices (monolithic device)
II. Chemically controlled systems
A. Bio-erodible systems
B. Pendant chain systems
III. Swelling controlled systems
IV. Magnetically controlled systems
20

21. • RAMS AND SLOTS (1996): Depending on usage
I. PERSONALLY APPLIED (In patient home self-care)
A. NON-SUSTAINED SUBGINGIVAL DRUG DELIVERY
• Home oral irrigation
Devices with traditional jet tips
▫ Oral irrigator (Water Pik, Fort Collins)
▫ Soft cone-rubber tips (Pick pocket)
▫ Blunt tipped mental cannula connected to syringe or
oral irrigator
B. SUSTAINED SUBGINGIVAL DRUG DELIVERY
• (none developed to date)
21

22. 22
Water pik Soft cone
rubber tip

23. • II.PROFESSIONALLY APPLIED (In dental office)
A.NON-SUSTAINED SUBGINGIVAL DRUG DELIVERY
Professional pocket irrigation
• Syringe with blunt end needle.
• Blunt-tipped cannula attached to oral irrigator
• Ultrasonic scaling devices
• Thin ultrasonic scaling inserts.
B.SUSTAINED SUBGINGIVAL DRUG DELIVERY
Controlled release devices:
• Reservoirs without a rate-controlling system: Hollow fibers, gels,
dialysis tubing
• Reservoirs with a rate-controlling system: coated drug particles,
microporous polymer membranes, monolithic matrices, erodible
polymeric matrices.
• Hybrids
23

24. • III. OTHER LOCAL DELIVERY METHODS:
Dentifrices, mouthrinses, chewing gum, Keyes technique, root
biomodification.
24

25. Antimicrobial effects of local
delivery devices:
• A study by Johnson et al. showed that better clinical and
microbiologic outcomes were obtained by combining
mechanical debridement with local delivery of the
antimicrobial. This established the key role of mechanical
debridement in successful clinical strategies for application of
local delivery devices (Johnson et al. 1998).
25

26. • With the most effective devices (those delivering high
concentrations of intrinsically efficacious antimicrobials for >1
week), suppression of 99–99.9% of total microbial load was
reported, leading to effective disinfection of the treated periodontal
pocket.
• After exhaustion of the drug reservoir, however, rapid
recolonization was observed. Three possible sources for this
recolonization were hypothesized:
(1) regrowth from the residual microbiota from within the periodontal
pocket;
(2) recolonization from other intraoral areas of infection; and/or
(3) re‐infection of the patient from other subjects.
26

27. • A pilot study conducted at the Forsyth Institute in 1988 by the
Goodson group started to address the question of the source
of recolonization (Holborow et al. 1990; Niederman et al.
1990).
• The study employed tetracycline fibers and SRP with or
without chlorhexidine mouth rinsing to complete the
treatment of the subjects who had participated in the pivotal
study leading to FDA approval of tetracycline fibers (Goodson
et al. 1991).
27

28. • The hypothesis was that the intraoral antibacterial effect of
chlorhexidine would modulate bacterial recolonization of
tetracycline fiber‐treated pockets.
• Results showed that chlorhexidine mouth rinsing over a
28‐day period led to significant depression of the bacterial
recolonization profiles for three target pathogens.
• The data were interpreted as an indication that the overall
oral ecology of the patient was a critical determinant of
success with this therapeutic modality.
28

29. • Persistent, stable suppression of bacterial levels was observed
in the full‐mouth disinfection group.
• Interestingly, early recolonization kinetics predicted clinical
(reduction of pocket depth and bleeding on probing) and
radiographic (hard and soft tissue subtraction analysis)
outcomes 3 and 6 months later (Tonetti et al. 1995).
29

30. 30

31. • Several important conclusions were drawn from these studies
and these represent important strategic elements for the
rationale use of local delivery devices:
1. Effective local delivery devices have the potential to
dramatically change the microbial profile of treated
periodontal pockets. Recolonization, however, is a critical
phenomenon that may undermine clinical benefit.
31

32. 2.Bacteria present in other areas of the mouth are the major
source of recolonization and need to be addressed by
improved oral hygiene measures, treatment of the whole
dentition, and – perhaps – antimicrobial mouth rinsing.
3.Local delivery devices are not a promising treatment for
subjects who are unable or unwilling to achieve improved
(optimal) oral hygiene levels.
32

33. Efficacy of local delivery devices:
• A systematic review and meta‐analysis by Hanes and Purvis
(2003) along with a more recent one by Matesanz‐Pérez et al.
(2013) represent the major evidence base for the use of local
delivery devices.
• The 2003 review, conducted for the American Academy of
Periodontology workshop, examined the clinical outcomes of
32 studies incorporating 3705 subjects and established that
adjunctive local drug delivery resulted in significant
reductions in gingival inflammation and probing depths, and
improvements in clinical attachment level.
33

34. • It observed clinical improvements for the adjunctive
application of minocycline gel, microencapsulated
minocycline, doxycycline gel, and chlorhexidine chips.
• Few studies have addressed the management of furcation
defects with local delivery devices. Shortterm (3–6 months)
adjunctive benefits in controlling gingival inflammation as
well as improvements in probing depths and clinical
attachment levels have been reported (Tonetti et al. 1995;
Dannewitz et al. 2009).
34

35. • Another interesting and rapidly emerging area of application
of local delivery devices relates to the control of peri‐implant
infections, particularly periimplantitis.
• Two independent systematic reviews on effective
interventions for peri‐implantitis (Esposito et al. 2012;
Muthukuru et al. 2012) identified some initial evidence that
local delivery combined with subgingival debridement may be
of greater benefit than subgingival debridement alone.
35

36. Clinical indications for treatment of
periodontitis with adjunctive local
delivery devices:
• The majority of studies assessing the adjunctive benefit of
local delivery devices to mechanical debridement have
identified a range of clinical conditions where the addition of
these devices leads to improved outcomes (Tonetti et al. 1994;
Tonetti 1998; Greenstein & Tonetti 2000).
• These include special local conditions and special patient
groups.
36

37. Local conditions:
• As the majority of untreated shallow (4–5 mm) pockets are expected
to heal with mechanical debridement alone, local delivery devices
are of potential benefit for deeper pockets (6–8 mm range) or
furcation involvements (Tonetti et al. 1998; Dannewitz et al. 2009).
• In this respect, local delivery may be advantageous in the
management of local non‐responding sites or disease recurrence
during supportive periodontal care.
37

38. • Another potentially important application is when residual
pockets are present in the so‐called esthetic zone where a
surgical intervention may compromise esthetics or phonetics.
• Application of local delivery devices seems to be a rationale
choice at sites with deep pockets and persistent bleeding on
probing that are associated with intrabony defects after
completion of the cause‐related phase of therapy.
38

39. Special patient groups:
• From a clinical standpoint, important attenuations of the
expected benefits of non‐surgical and surgical treatment have
been observed in high‐risk groups.
• These include smokers and subjects with diabetes, significant
co‐morbidities or erratic compliance with oral hygiene and/or
long‐term adherence to the necessary supportive periodontal
care program.
39

40. • Studies have reported that the adjunctive effect of local drug
delivery may not be adversely affected by cigarette smoking
(Ryder et al. 1999).
• In a planned secondary analysis of a multicenter trial
assessing the adjunctive benefits of minocycline
microspheres, the enhanced response to local delivery device
application was greatest among smokers (Paquette et al.
2003, 2004).
40

41. LDD in treatment of peri-implantitis:
• CIST protocol: Depending on
the clinical and the
radiographic diagnosis, a
protocol of therapeutic
measures, called cumulative
interceptive supportive
therapy (CIST), has been
designed to head off the
development of peri-implant
lesions.
41

42. • Antibiotic treatment (supportive therapy protocol C):the
application of local antibiotics through the use of controlled
delivery devices has emerged as a suitable treatment concept.
• However, only release devices with adequate release kinetics
may be used to ensure successful clinical outcomes.
• Tetracycline periodontal fibers (Actisite®; Alza, Palo Alto,
CA, USA) have successfully been applied in some case studies.
The therapeutic effect appears to be identical to the effect
documented for the systemic administration of
antibiotics.(Mombelli et al. 1998)
42

43. • Control release device consists of microspheres containing
minocycline hyclate (Arestin®; Johnson & Johnson) which
are applied to the peri-implant pocket using a syringe.
• These beads remain sticking to the implant surface and soft
tissue walls for at least 10 days and, hence, provide an ideal
profile for a high-dose application at the site.
• Several clinical studies have documented the efficacy of the
product on both the clinicaland the microbiologic level.
(Renvert S et al 2006 & 2008, Salvi GE et al. 2007, Perrson
GR et al. 2006)
43

44. Antimicrobial agents used for LDD:
• Tetracyclines: Tetracycline-HCl, doxycycline hyclate and
minocycline-HCl, are broad-spectrum antibiotics active
against both gram-positive and gram-negative bacteria.
• Minor alterations in the molecular structure make both
doxycycline and minocycline more lipophilic than the parent
compound, resulting in better adsorption following systemic
delivery and better penetration into the bacterial cell.
44

45. • The tetracyclines bind to the bacterial 30S ribosomal subunit
and inhibit protein synthesis in the bacterial cell. Thus, these
are normally bacteriostatic antibiotics.
• At high concentrations, such as those achieved with localized
delivery of the antibiotic directly into the periodontal pocket,
the tetracyclines may exert a bactericidal effect due to their
ability to cause alterations in the cytoplasmic membrane.
• This may result in leakage of nucleotides and other
components from the bacterial cell and result in its death.
45

46. • LDD systems like tetracycline, 12.7 mg tetracycline- HCl in an
ethylene ⁄vinyl acetate copolymer fiber (Actisite®), and doxycycline,
10% doxycycline hyclate in a gel delivery system (Atridox®).Both
systems, in a number of clinical trials, have been demonstrated to
give statistically significant improvements in clinical (attachment
level and probing pocket depth) and microbial parameters over
those obtained with mechanical debridement alone [Drisko CL et al
1998, Garret et al 1999,2000, Muller et al 1993].
• Minocycline, the most lipophilic of the tetracyclines, has also been
incorporated into a local delivery device consisting of minocycline-
HCl microspheres (Arestin®) and Periocline® which is 2%
minocycline gel use for local application.
46

47. 47
Armamentarium and application
of tetracycline fibres.
Minocycline
microspheres

48. • Collagenase inhibitors: A series of double-blind, placebo-
controlled clinical trials has demonstrated that
subantimicrobial dose doxycycline (SDD), 20 mg bid
(Periostat®), produces an improvement in clinical indices
(Ashley RA et al 1999,Caton JG et al 2000 & 2001, Crout RJ et
al 1996, Golub in 1995), without causing any detectable effect
on the subgingival flora or an increase in antibiotic resistance.
• Significant improvements in clinical attachment level and
pocket probing depth were present at 3, 6, and 9 months of
treatment in subjects that received SRP and SDD compared to
SRP alone.
48

49. • It is not surprising that SDD exerted no detectable effect on
the normal flora at any of these sites. SDD at 20 mg bid yields
peak serum levels of 0.7–0.8 µg of doxycycline per ml and
steady state concentrations of around 0.4 µg ⁄ml.
49

50. • Penicillins: The penicillins are a broad class of antibiotics that
inhibit bacterial cell wall synthesis and directly result in the
death of the cell. All penicillins consist of a β-lactam ring, a
thiazolidine ring, and an acyl side chain.
• Amoxicillin, a semisynthetic penicillin, has excellent activity
against both gram-negative and gram-positive bacteria, is
absorbed well following oral administration, and penetrates
into the gingival crevicular fluid.
50

51. • Augmentin®, introduced a little over a decade ago, combines
the antibiotic amoxicillin with a β -lactamase inhibitor,
clavulanic acid. Clavulanic acid exhibits no antimicrobial
activity, but it does contain an unprotected β -lactam ring.
• Bacteria normally resistant to amoxicillin due to the
production of β -lactamase may be susceptible to the
combination of amoxicillin and clavulanic acid.
51

52. • The efficacy of Augmentin® has been tested in a few clinical trials
with conflicting results. Magnusson et al. (1989) reported, for sites
deemed clinically active, an average 2 mm gain in clinical
attachment 3 months post-therapy and an average decrease of 2.5
mm probing pocket depth 6 months post-therapy.
• Winkel et al.(1999) in double-blind, placebo-controlled study with
21 patients with a diagnosis of generalized adult periodontitis found
that, in comparison with placebo, Augmentin® provided no
additional clinical or microbiological benefits.
52

53. • Clindamycin: Clindamycin is bacteriostatic and inhibits
bacterial protein synthesis by binding to the 50S ribosomal
subunit.
• Clindamycin-HCl has been shown, following normal oral
dosage, to penetrate into the gingival crevicular fluid and to
achieve and maintain concentrations that exceed the MICs of
the periodontopathic gram-negative anaerobic
bacteria.(Walker CB et al 1981)
53

54. • Studies by Gordon J et al. (1985,1990), Magnusson et al.
(1994), Ohta Y et al (1986) suggest clindamycin-HCl may be a
useful adjunct in the treatment of truly refractory patients
who have not responded favorably to other modes of
periodontal therapy.
• Prior to initiating clindamycin therapy, culture and sensitivity
testingis strongly recommended to screen for the presence of
E. corrodens (Walker CB et al. 1996) and A.
actinomycetemcomitans (Loesche WJ et al. 2002). Presence
of either contraindicates clindamycin use.
54

55. • Following clindamycin initiation, patients should be carefully
monitored and advised of the possibility of adverse
gastrointestinal events.
• Due to the potential serious adverse effects, the use of this
drug should be reserved for those patients that have proven to
be refractory to other modes of periodontal therapy.
55

56. • Azithromycin: Azithromycin belongs to the same general class
of macrolide antibiotics as erythromycin.
• Azithromycin has been reported to penetrate both healthy and
diseased periodontal tissues and to maintain
chemotherapeutic levels in excess of the MICs of the majority
of periodontopathogens thought to be involved in chronic
inflammatory periodontal diseases.
• Smith et al. (2000) conducted a double-blind, placebo-
controlled clinical trial to evaluate the efficacy of azithromycin
as an adjunct to SRP.
56

57. • Metronidazole: A 5-nitroimidazole compound, specifically
targets anaerobic microorganisms but has essentially no
activity against aerobic or microaerophilic bacteria.
• Localized delivery of metronidazole to specific, diseased sites
would allow minimal amounts of drug to achieve high
concentrations.
• Elyzol®, which is commercially available in many European
countries but not in the United States. Elyzol® is a 25%
metronidazole dental gel consisting of metronidazole
benzoate in a mixture of mono- and triglycerides.
57

58. • Metronidazole benzoate gradually disintegrates into
metronidazole and delivers high concentrations of the drug to
the periodontal pocket for approximately 24 h after
placement.
• Riep et al.(1999) compared the effects obtained with the
dental gel plus SRP, to SRP alone, in 30 maintenance patients
in a single-blind clinical study. Both treatments resulted in
significant improvement in probing pocket depths and clinical
attachment level. However, there were no significant
differences between the two treatments.
58

59. 59

60. • Chlorhexidine: Chlorhexidine has often been employed as an
adjunct to mechanical debridement due to its broad-spectrum
antimicrobial activity, substantivity in the oral cavity and ease
of use during oral irrigation or gel placement.
• A biodegradable chlorhexidine containing gelatin chip
(PerioChip®) has received Food & Drug Administration
approval in the United States for use as an adjunct to SRP.
60

61. • The results of a multicenter clinical trial reported that the
chip’s use resulted in a significant improvement in probing
pocket depth relative to SRP alone but that no significant
differences were noted in change in clinical attachment level
(Jeffcoat et al 1998, Soskolne WA et al 1997). Reductions in
levels of P. gingivalis, P. intermedia, T. forsythia, and C. rectus
were reported relative to SRP.
• However, Daneshmand et al.(2002) did not find any
microbial benefit when the chlorhexidine chip was used as an
adjunct to SRP compared to SRP alone.
61

62. • The gelatin chip is placed
directly into the periodontal
pocket, releasing 2.5 mg of
chlorhexidine over a period
of 7–10 days. Chlorhexidine
levels, within the pocket,
reach an average
concentration equivalent to
125 µg of chlorhexidine per
ml of gingival crevice fluid.
62

63. • 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.
• 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.
63

64. • 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.
64

65. • Povidone-iodine: Povidone-iodine (PVP-iodine) is a
bactericidal antiseptic whose mechanism of action includes
oxidation of amino, thiol, and hydroxy moieties of amino
acids and nucleotides.
• Greenstein et al in 1999, in a recent review of the effects of
PVP-iodine, found evidence indicating PVP-iodine irrigation,
delivered to the periodontal pocket via ultrasonic scalers,
achieved better results in deep pockets than water.
65

66. • Rosling et al.in 1986 tested the efficacy of PVP-iodine as an
adjunct to conventional, nonsurgical periodontal therapy and
retreatment in 223 advanced periodontitis subjects. During
the 12 years of maintenance therapy, a larger proportion of
the PVP-iodine-treated subjects maintained shallow pockets,
avoiding further loss of attachment relative to mechanical
debridement alone.
• In conclusion, documented evidence indicates that a
beneficial additive effect may be obtained utilizing PVP-iodine
as an adjunct to mechanical periodontal therapy.
66

67. Other Agents Tried As LDD:
• Eucalyptus Extract: Nagata et al 2008
• Neem Extract: Ravindra Pai et al 2004
• Herbal Combinations: Reddy et al 2010
• Simvastatin: Morris et al 2008
• Growth Factors: Cooke et al 2006
• Chitosan-PVA-based local delivery system: Wang LC et al
2010
• Curcumin: Elavarasu S et al 2016
• Atorvastatin: Garg S et al 2016
67

68. Conclusion:
• Local drug delivery into the periodontal pocket is an effective
treatment adjunct to mechanical debridement.
• Clinical application requires the use of a well‐designed technology
platform that is able to counteract GCF clearance of the locally
applied antibiotic and maintain effective concentrations for long
enough for the desired pharmacologic effect to occur.
• Pocket disinfection is feasible, but recolonization is a critical
phenomenon that needs to be prevented with a specific clinical
strategy: optimal supragingival hygiene, full‐mouth approach,
and/or use of an antiseptic mouth rinse.
68

69. BIBLIOGRAPHY:
• Periodontology 2000:systemic & topical antimicrobial therapy in
periodontics. February 1996 - vol. 10 issue 1 page 5-159
• Periodontology 2000:‘nonsurgical periodontal therapy’ :October
2004, vol 36, issue 1, page no 9-204
• Jan lindhe; Clinical periodontology and implant dentistry: 6th
edition: chp 44; 891-97
• Carranza 12 edition: Chp 89.
• Stuart froum:Dental impalnt complications:etiology, prevention and
treatment: Chp 7: 119-33
• Arvind venkatesh :local drug delivery systems in the treatment of
periodontitis – an overview; international journal of pharmacy and
pharmaceutical sciences ,vol 4, issue 1, 2012 ;30-7
• Esha agarwal: Locally delivered 0.5% azithromycin, as an adjunct
to non surgical treatment in chronic periodontitis with type 2
diabetes: A randomized controlled clinical trial:journal of
periodontology ;2012:1-11
69