basic concepts in local drug delivery in dentology

1. LOCAL DRUG DELIVERY
SYSTEMS
1
BY: DR.KINJAL GABANI
PART III

2. CONTENTS Introduction
 Historical perspective
 Terminology
 Objectives
 Indications
 Contraindications
 Advantages
 Disadvantages
 Systemic Versus Local Drug Delivery
 Requirements For Local Antimicrobial Agents
 Factors Affecting the Bio-availability of an antimicrobial agent
 Classification of local antimicrobial therapy in periodontics
 Drug delivery systems
 Local Drug Delivery’s Impact on Deep Probing Depths (≥7 mm)
 Inhibition of Periodontal Disease Progression
 Impact of Local Drug Delivery on Furcations
 Repair of Osseous Defects
 Future trends
 Conclusion
2

3. INTRODUCTION:
3

4. addition of antimicrobials (systemic and local)
adjuncts to mechanical therapy.
4
Systemic
antimicrobial
agents
Adverse
effects
Local drug
deliveries

5. HISTORICAL PERSPECTIVE:
 W.D. Miller in the 1880’s suggested the use of an
antimicrobial mouthrinse (Listerine) to aid in fighting what
was then known as ‘Pyorrhea alveolaris’.
 The concept of targeted drug delivery had its origin in the
1970’s based on the theory that if one could substantially
improve the cellular specificity of a drug there would be
an accompanying significant improvement in the
therapeutic index; i.e, efficacy to side effects.
 Dr. Max GoodSon (1979) first proposed the concept of
controlled release local delivery of therapeutic agents for
the treatment of periodontitis.
5

6. TERMINOLOGY:
 Antimicrobial agents are chemotherapeutic agents that reduce
the amount of bacteria present either by superficially targeting
certain organisms or by nonspecifically reducing all bacteria.
 Targeted drug delivery: refers to delivery of medication to a
patient in a manner that increases the concentration of the
medication in some parts of the body relative to others.
 Local delivery of antimicrobial agents in periodontics
Implies antimicrobial therapy placed directly in the subgingival
region. The term local delivery is usually used to suggest more
specific or targeted delivery of an agent.
 Non-sustained subgingival drug delivery Provides high pocket
concentrations of the antimicrobial agent for only short time periods.
6

7.  Sustained subgingival drug delivery/ Controlled
release delivery (CRD)
Synonyms: Sustained release, Prolonged release,
timed release, slow release, sustained action,
prolonged action or extended action.
CRD’s are designed to release a drug slowly and to
retain therapeutic level for a prolonged period of
time.
7

8. ADVANTAGES:
 Higher concentrations.
 Broad spectrum antiseptic solutions.
 Professionally applied antimicrobial regimens reduce
potential problems with patient compliance.
 Local antimicrobial delivery reduces the dangers
associated with systemic administration such as toxicity,
adverse reactions, resistant strains and superimposed
infections.
8

9. INDICATIONS:
 Isolated periodontal pockets (>5mm), with successful phase I
therapy.
 Periodontal patients who are medically compromised where
surgical therapy is contraindicated.
 In combination with mechanical debridement or alone.
 In patients who are suffering from recurrent or refractory
periodontitis.
 During periodontal regenerative procedures.
 Where periodontal surgery is to be avoided or the patient is on
supportive periodontal treatment.
9

10. DISADVANTAGES:
 Difficulty in placing antimicrobial agents into deeper
parts of pockets and furcation lesions.
 Patient compliance and manual dexterity.
 Time consuming in patients with numerous advanced
lesions.
 Do not markedly affect pathogens residing on other oral
surfaces.
 Non-sustained drug delivery provides only a brief
exposure of the target microorganism to the applied
antimicrobial agent.
10

11. Systemic Local
1. Route of administration
2. Pain/Discomfort
3. Drug dosage
4. Peak levels
5. Pharmacokinetics
6. Frequency
7. Super infection
8. Microbial resistance
Oral or Parental
Not painful
Higher drug dosage
(in mg)
Few hours in plasma
Distribution in various
compartments where
antimicrobial effect may
not be required.
Once in 6-12 hours
Present
Present
Site Specific
Nil
Lower dosage
(in micrograms)
Within few minutes in GCF
Minimal body distribution
to different compartments
with maximum concentration
at delivered sites.
Usually once a week
Limited
Limited
11

12. Systemic Local
9.Patients compliance
10.Time required
11. Side effects
12. Effects on connective
tissue associated
plaque
Required for better
efficacy
Less time
More
Effective
Patient delivered -
compliance required
Professional Delivered -
not required
Longer time if many sites
are involved
Limited
Limited
12

13. REQUIREMENTS FOR LOCAL ANTIMICROBIAL AGENTS
 Safety
 Stability
 Substantivity
 Adequate subgingival delivery
 Achievement of effective concentrations
 Biodegradable
 No emergence of bacterial resistance
 Should be effective only against periodontal
pathogens.
 Cost-effectiveness.
13

14. RAMS AND SLOTS (1996)
- depending on usage
I. PERSONALLY APPLIED
by patient at home (self-care)
A. NON-SUSTAINED SUBGINGIVAL DRUG DELIVERY
Home oral irrigation
Home oral irrigation devices:
 Devices with traditional jet tips
 Oral irrigator
 Soft cone-rubber tips
 Blunt tipped metal cannula connected to syringe or oral
irrigator
B.SUSTAINED SUBGINGIVAL DRUG DELIVERY
(none developed to date)
14
CLASSIFICATION OF LOCAL ANTIMICROBIAL THERAPY IN
PERIODONTICS

15. II. PROFESSIONALLY APPLIED (In dental office)
A. NON-SUSTAINED SUBGINGIVAL DRUG DELIVERY
Professional pocket irrigation devices :
 Syringe with blunt end needle
 Blunt-tipped cannula attached to oral irrigator
B. SUSTAINED SUBGINGIVAL DRUG DELIVERY
Controlled release devices:
15

16. Fibers
Several polymers such as
 poly(ecaprolactone) (PCL),
 polyurethane,
 polypropylene,
 cellulose acetate propionate
and
 ethyl vinyl acetate (EVA)
have been investigated as
matrices for the delivery of
drug
to the periodontal pocket.
Examples are tetracycline
fibers.
16

17. Films
 Films are matrix delivery systems in which drugs are
distributed throughout the polymer and release occurs
by drug diffusion and/or matrix dissolution or erosion.
 Film is prepared either by solvent casting or direct milling.
17

18.  Bigger films either could be applied within the cavity
onto the cheek mucosa or gingival surface or could
be cut or punched into appropriate sizes so as to be
inserted into the site of action.
18

19.  Sustained release devices composed of cross-linked fish
gelatin (bycoprotein) containing chlorhexidine
diacetate or chlorhexidine hydrochloride have been
developed by Steinberg.
19

20. Injectable System
 The application can be easily
and rapidly carried out,
without pain, by using a
syringe.
 Thus, the cost of the therapy is
considerably reduced
compared to devices that
need time to be placed and
secured.
20

21. Gels
 Mucoadhesive, metronidazole (MTZ) containing gel
systems based on hydroxyethyl cellulose, corbopol 974,
and polycarbophil have been made.
 Gel is applied sublingually with the help of blunt cannula
and syringe.
 Locally applied controlled release DOX gel may partly
counteract the negative effect of smoking on
periodontal healing following no surgical therapy.
21

22.  Tetracycline containing copolymer gels represents a
safe and effective bioerodible therapy for periodontitis
due to
 Safety profile,
 Longer-term retention,
 Antimicrobial activity.
22

23. Strips and Compacts
 Acrylic strips have been fabricated using a mixture of polymers,
monomers and different concentrations of antimicrobial
agents.
 Strips were fabricated either by solvent casting or pressure melt
method.
 Strips containing tetracycline, metronidazole or chlorhexidine
demonstrated a decrease in number of motile rods, notably
spirochetes.
 In a later development, the evaluation of amoxycillin-clavulanic
acid loaded acrylic strips is reported.
23

24. Microparticle System
 Microparticles based system of biodegradable poly
alpha hydroxy acids such as poly lactide (PLA) or poly
(lactide – co-glycolide) PLGA containing tetracycline
has been designed for periodontal disease therapy.
 PLGA microspheres containing minocycline have been
formulated and have been used for the elimination of
Porphyromonas gingivalis from the periodontal pocket .
24

25. Dentifrices, mouthrinses, and
chewing gum
 These are inefficient delivery systems because they fail to direct
drugs into the periodontal pocket.
 Dentifrices containing chemotherapeutic agents such as
triclosan chlorhexidine, stannous fluoride and flurbiprofen provide
limited benefit in the treatment of periodontitis.
 Mouthrinses have been tried with various antimicrobial agents.
The most effective in reducing gingivitis have been found to be
chlorhexidine gluconate and listerine.
25

26. Keyes Technique
The keyes technique involves the application by tooth brushing
of a slurry of sodium bicarbonate and hydrogen peroxide for the
control of plaque microorganisms.
Many studies have been conducted to evaluate this treatment
modality, but the results have shown that it is no more effective
than conventional oral hygiene.
26

27. • LOCAL DRUG DELIVERY AGENTS
 Tetracycline
 Doxycycline
 Minocycline
 Chlorhexidine
 Metronidazole
27

28. TETRACYCLINE
 The tetracyclines were introduced into clinical practice
in the late 1940s.
 They are primarily bacteriostatic agents that are
effective against many Gram negative species
including putative pathogens such as Aggregatibacter
actinomycetemcomitans.
 They interfere with bacterial protein synthesis and also
inhibit tissue collagenase activity.
28

29.  Tetracyclines are used extensively in the management
of periodontal diseases and the agents used commonly
are
 Tetracycline HCl,
 Doxycycline HCl,
 Minocycline HCl.
 Most of the subgingival microorganisms are susceptible
to tetracycline at a minimum inhibitory concentration
(MIC) of ≤ 1-2 µg/ml.
29

30. Actisite (US ; Switzerland )
 The first delivery devices involved hollow fibers of
cellulose acetate filled with tetracycline.
 These are non-resorbable biologically inert,
generally considered as safe, plastic copolymer
(ethylene and vinyl-acetate) loaded with 25%
w/w tetracycline HCl powder packaged as a
thread of 0.5 mm in diameter and 23 cm in
length.
 Fiber is packed into pocket and secured with a
thin layer of cyanoacrylate adhesive, left in
place for 7-12 days.
30

31. 31

32. 32

33.  Recently bioresorbable tetracycline fiber
has been developed with base of collagen
film, which is commercially available as
PERIODONTAL PLUS AB.
 It offers the advantage of no second
appointment for removal as it biodegrades
within 7 days.
33

34. Tetracycline
fiber
Systemic
adm
GCF
Conc
1590 µg/ml 4-8 µg/ml
Serum
conc
0.4 µg/ml 2-4 µg/ml
34

35. Gel
 Tetracycline-Serratiopeptidase-Containing Periodontal
Gel Formulation has shown statistically significant results
along with scaling and root planing.
35

36.  In a 60-day multicenter study - 107 periodontitis patients
after supragingival scaling, (Goodson et al 1991)
 Four non-adjacent teeth with pockets in the range of 6-
10mm was selected
 Randomly assigned to-
Tetracycline fiber
Placebo fiber
Scaling
Untreated
Analysis: probing depth (1.5-2 mm),
gain of attachment level (0.6 - 1.0 mm)
36

37.  Newman et al (1994) Conducted a study in
periodontal maintenance patients needing treatment of
localized recurrent periodontitis. Effect of fiber therapy
was evaluated as an adjunct to SRP. Results – sites
treated with fiber and SRP showed significantly higher
attachment level, pocket depth reduction and less BOP.
significant (P = 0.001) reduction in probing depth
(1.9 and 1.8 mm), gain of attachment level (1.6 and
1.0 mm) and reduction of BOP (38.1% and 33.3%) for
test and control sites, respectively at 6 months.
37

38.  Williams,Lana S. Krause,and William J. Killoy studied
and they concluded that multiple strips are superior to
a single strip in reducing bleeding on probing, and
that local delivery of tetracycline is superior to root
planing alone in reducing probing depth.
 J. Max Goodson evaluated maintainence response of
Periodontal Treatments Using Controlled-Release
Tetracycline Fibers and concluded that compared to
scaling, Fiber therapy for 10 days, or Fiber therapy for
20 days, scaling and root planing in conjunction with
tetracycline fiber therapy for 10 days can significantly
reduce disease recurrence 3 to 12 months following
treatment in the absence of supportive care.
38

39.  M. Minabe, K. Takeuchi et al (1989) evaluated the
duration of therapeutic effect after administration of
the collagen film immobilized tetracycline (TC film). TC
film or tetracycline non-immobilized placebo film was
applied one time to the periodontal pocket (4 mm) of
five periodontitis patients (20 teeth). The clinical an
microbiological effects are summarized as follows: The
group that received TC film continued to show
significantly low values for bleeding upon probing the
pocket depth for 3 and 4 weeks, respectively.
39

40. MINOCYCLINE
 Semisynthetic tetracycline - was first introduced in
1967
 Minocycline hydrochloride has in vitro antibacterial
activity against a wide range of gram-ve and
gram+ve microorganisms thought to be related to
periodontal disease.
 Local delivery of minocycline has been tried clinically
via three different modes i.e. film, microspheres, and
ointment.
40

41. Film
 Ethyl cellulose film containing 30% of Minocycline were
tested as sustained release devices.
 The results indicated that the use of this device may
cause complete eradication of pathogenic flora from
the pocket after 14 days.
41

42. Microsphere
 The FDA recently approved a new, locally delivered,
sustained release form of minocycline microspheres
(ARESTIN) for subgingival placement.
 The 2% minocycline is encapsulated into bioresorbable
microspheres (20-60μm in diameter) in a gel carrier and
has resorption time of 21 days.
 Gingival crevicular fluid hydrolyses the polymer and
releases minocycline for a period of 14 days or longer
before resorbing completely.
42

43. 43

44. Ointment
 Dentomycin (2% Minocycline gel) has received
regulatory approval for the treatment of periodontitis in
the European Union.
 The concentration of minocycline in the periodontal
pocket is about 1300μg/ml, 1 hr after single topical
application of 0.05 ml ointment (1mg of minocycline)
and is reduced to 90μg/ml after 7 hrs.
44

45.  Laurell L104
performed a study to determine the
effect of repeated placement of minocycline
microspheres on probing depth reductions in
periodontal therapy. 748 patients with moderate
to advanced periodontitis
 When compared to scaling, the minocycline microspheres
group displayed a significantly greater reduction in
probing depth of 0.3mm.
45

46. DOXYCYCLINE
 Doxycycline is a broad-spectrum semi synthetic
tetracycline.
 Doxycycline is bacteriostatic, inhibiting bacterial
protein synthesis due to disruption of transfer RNA
and messenger RNA at ribosomal sites.
Biodegradable formulation contains:
 10% by weight Doxycycline
 33% by weight poly (DL- lactide)
 57% by weight NMP (N-methyl-2-pyrrolidone)
46

47. The ATRIDOX® product(US) is a subgingival
controlled-release product composed of a
2 syringe mixing system.
47
Syringe A contains 450 mg of the
ATRIGEL® Delivery System, which is a
bioabsorbable, flowable polymeric
formulation composed of 36.7% poly (DL-
lactide) dissolved in 63.3% N-methyl-2-
pyrrolidone

48. 48
Syringe B contains doxycycline
hyclate which is equivalent to 42.5
mg doxycycline.

49. The constituted product is a pale yellow to
yellow viscous liquid with a concentration
of 10% of doxycycline hyclate
49

50. 50

51. Doxycycline levels in GCF Time
1,500 - 2000 μg/mL 2 hours
> 1000 μg/mL 18 hours
Well above the minimum inhibitory
concentration for
periodontal pathogens (6.0 μg/mL)
Day 7
95% of the polymer is bio absorbed
or expelled from the pocket
naturally
Day 28
51

52.  Machion L and Carleto A et al conducted a study to study the
effects of locally delivered doxycycline as an adjunctive
therapy to scaling and root planing in the treatment of
periodontitis. locally delivered doxycycline (10%) with scaling
and root planing in the periodontal treatment. At 6 months,
the proportion of sites showing RAL gain of 1 to 2 mm was
36.8% versus 21.7% for SRP-D and SRP, respectively (P = 0.01).
 Garrett et al 1999, 2000 – 411 pts with moderate to severe
adult periodontitis. Atridox was compared to placebo control
and oral hygiene and SRP. Result : Treatment to be statistically
superior to placebo control and oral hygiene and equally
effective as SRP.
52

53. CHLORHEXIDINE
 Chlorhexidine gluconate is an antimicrobial agent
active against a wide spectrum of gram-positive
and gram-negative organisms, yeast, fungi,
facultative anaerobes and aerobes.
 Its mechanism of action relates to
 Reduction in pellicle formation,
 Alteration of bacterial adherence to teeth, and
 An alteration of bacterial cell walls, causing lysis.
53

54. PERIO-CHIP
 Unique patented “targeted
controlled release” bio
degradable polymer
containing chlorhexidine
(Israel).
 Small, bullet-shaped or
baby’s finger nail like thin film,
weighing 7.4mg.
 Measures 5x4 mm in size and
0.35 mm thickness.
 The chip contains 2.5 mg
chlorhexidine gluconate
incorporated in a
biodegradable matrix of
cross-linked hydrolyzed
gelatin.
54

55. 55

56.  Rodrigues G. and Luciana M et al (2007) evaluated
the effectiveness of a chlorhexidine chip in
maintenance therapy. After 6 months, a reduction in
PD of 2.64 ± 0.02 mm and 2.12 ± 0.02 mm was
observed for CHIP and SRP groups, respectively
(P>0.05). The observed gain in CAL was 2.19 ± 0.87 mm
and 2.07 ± 1.53 mm for CHIP and SRP groups,
respectively (P>0.05). In deep pockets, PD reduction
was 3.60 ± 0.70 mm for CHIP group and 2.83 ± 0.62 mm
for SRP group (P = 0.01).
56

57.  Michael S and Marjorie K et al (2003) performed a
study to test the hypothesis that adjunctive
subgingival administration of chlorhexidine gelatin
bioresorbable chips enhances bone gain when used
in conjunction with guided tissue regeneration. This
was a single centre, blinded, 2-arm parallel design
study of 44 subjects with one or more sites with probing
depth and clinical attachment loss ≥5 mm following
initial therapy and radiographic evidence of bone
loss. Subjects receiving sham chip placement gained
a mean bone height of 1.49 ± 0.22 mm, while patients
receiving the CHX chips gained significantly more
bone height (3.5 ± 0.45 mm; P<0.001).
57

58.  Soskolne et al 1997, Jeffcoat et al 1998 – split mouth design to
compare the treatment outcomes of SRP alone with the combined
use of SRP & PerioChip in pocket depth of 5-8mm. Results – average
PD reduction in treated sites of 2.5mm with chip was significantly
greater than in the sites receiving mechanical treatment only.
58

59. Periocol-CG
 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.
 It has been shown to resorb after 30 days; however their
coronal edge degrades within 10 days.
59

60. METRONIDAZOLE
 Metronidazole is particularly attractive as an
antimicrobial because of its selective efficacy against
obligate anaerobes.
 Both systemic and local applications are effective
against periodontal pathogens.
 Therefore, local application would be preferred.
 In the recent past, Metronidazole has been
incorporated as collagen sponges, dialysis tubing,
acrylic strips, films and gel forms for sustained
subgingival delivery in the treatment of periodontal
disease.
60

61. METROGENE (SEPTODENT, FRANCE)
 It is a new combination of two known substances;
bovine collagen (Type I) sponges into which
Metronidazole is incorporated at a concentration of
5 percent in the finished product.
 In contact with human gingival fluid, this collagen
rapidly forms a resorbable gel which is non-irritant as
it is virtually devoid of any immunogenicity (Hugly
1983, Stein 1985).
61

62. Elyzol (Copenhagen, Denmark)
 Metronidazole benzoate 25% in a mixture of glyceryl
mono-oleate and sesame oil.
 The gel disintegrates in the pocket and releases
Metronidazole.
 Estimated dose of Metronidazole per treated tooth
was 3mg and drug concentration in GCF after one
day was 1g/ml.
62

63. Local Drug Delivery’s Impact on Deep Probing
Depths (≥7 mm)
 As probing depths increase, SRP becomes less efficient;
therefore investigators evaluated the potential benefit of
employing local drug delivery at deep sites (≥7 mm).
 Timmerman et al.(1996) reported that there was no benefit
of employing 2% minocycline gel as an adjunct to SRP to
reduce probing depths at deep sites, whereas Van
Steenberghe et al.(1999) noted that combined therapy
provided a better result than SRP alone at sites ≥7 mm
deep.
63

64.  Magnusson (1998) performed a study to evaluate the topical use of
a metronidazole gel in the treatment of sites with symptoms of
recurring chronic inflammation Both treatments yielded a
statistically significant (P = 0.001) reduction in probing depth (1.9
and 1.8 mm), gain of attachment level (1.6 and 1.0 mm) and
reduction of BOP (38.1% and 33.3%) for test and sites, respectively
at 6 months.
64

65.  In summary, sites with deep probing depths provide
an opportunity to attain greater probing depth
reductions than shallow pockets.
 However, there are limited data related to the ability
of individual drug delivery systems to enhance
probing depth reductions at pockets ≥7 mm.
 Therefore, this facet of therapy requires further study.
65

66. Impact of Local Drug Delivery on Furcations
 Tonetti et al. (1998) reported that tetracycline fibers in
conjunction with SRP initially provided a better result
than SRP alone at molar furcations; however, after 6
months, there were no statistically significant
differences with respect to mean probing depth
reduction or gain of clinical attachment.
 In contrast, Williams et al. and Meimberg et al.(2002)
noted a statistically significant greater probing depth
reduction in molar furcation when SRP plus minocycline
microspheres were compared to SRP alone.
 Additional studies are needed to assess the effect of
local delivery in a variety of defects to include
furcations and intrabony lesions.
66

67. Future trends in local drug
delivery
1. Clarithromycin gel
• A study has been conducted to investigate the
adjunctive effects of subgingivally delivered 0.5 %
clarithromycin as an adjunct to scaling and root planing
for treating chronic periodontitis smoker subjects.
• It was observed that the adjunctive use of 0.5%
clarithromycin as a controlled drug delivery system
enhanced the clinical outcome.
• This product is still under investigation and yet to be
patented.
67

68. 2. Herbal products
 Various herbal formulations like aloe vera,
neem, tulsi, propolis, cocoa husk,
pomegranate, cranberry etc. are being
used widely these days.
 These products have shown promising results
with no side effects and are economical as
well.
68

69. The strategic approaches with associated
challenges and achievements towards
the formation of periodontal drug delivery
system :
Strategy 1: systemic delivery devices
 Low benefit to risk ratio, ingestion of large drug
doses
 Inadequate drug concentration at periodontal site
 Rapid/non-sustained drug release
 Poor patient compliance: frequent
administration
 No penetration of delivery system
 No adhesion/retention into periodontal pocket
 High incidence of bacterial resistance
69

70. Strategy 2: local mouth rinses and dental irrigation
 Inadequate drug concentration at periodontal site
 Drug dose is reduced
 Rapid/non-sustained drug release
 Systemic toxicity is decreased
 Poor patient compliance: frequent administration
 No penetration of delivery system
 No adhesion/retention into periodontal pocket
 High incidence of bacterial resistance
70

71. Strategy 3: non-biodegradable, intrapocket fibres, strips, films
and microparticles
 Poor patient compliance: discomfort during the placement of
device, at least two visits to therapist is required and
development of foreign body response, if left in situ
 Adequate drug concentration at periodontal site
 Poor penetration of system/drug
 Prolonged/sustain drug release
 Poor retention of system into periodontal pocket
 Less frequent administration
 Low incidence of bacterial resistance
71

72. Strategy 4: biodegradable, intra-pocket fibres,
strips, films and microparticles
 Poor patient compliance: discomfort during
placement
 Visit to therapist is reduced
 Poor penetration of system/drug
 No foreign body response
 Poor retention of system into periodontal pocket
 Low incidence of bacterial resistance
72

73. Strategy 5: biodegradable nanoparticles
 Poor retention of system into periodontal
pocket
 Placement is easier
 Low incidence of bacterial resistance
 Good penetration due to nano-sized
particles
73

74. Strategy 6: Mucoadhesive, biodegradable nanoparticles
 Low incidence of bacterial resistance
 Good retention of system
Strategy 7: antibiotic-free, mucoadhesive, biodegradable
nanoparticles
 Bacterial resistance does not develop
74

75. CONCLUSION
 Local drug delivery often appears to be as
effective as scaling and root planing with
regards to reducing signs of periodontal
inflammatory disease.
 Local delivery may be an adjunct to the
conventional therapy. The sites most likely to be
responsive to this adjunctive treatment method may
have refractory or recurrent periodontitis, or specific
locations where it is difficult to instrument root
surfaces.
75

76. REFERENCES
 Carranza’s Clinical Periodontology 10th
Ed.
 Pramod Vishwanath Prasad et al. Bird’s Eye View on the
Recent Advances in Drug Delivery Systems. Journal of
Biomaterials and Nanobiotechnology, 2011, 2, 544-556
 Vidya Dodwad et al. Magic Bullet to treat Periodontitis:
A targeted approach. JPBMS, 2012, 20 (19)
 Amit Bhardwaj et al. Advances in periodontal drug
delivery systems. International Journal of Novel Drug
Delivery Technology. Jan-Mar 2012, Vol-2, Issue-1
76

77.  Vidya Dodwad et al. Local Drug Delivery In Periodontics:
A Strategic Intervention. International Journal of
Pharmacy and Pharmaceutical Sciences. Vol 4, Issue 4,
2012
 Pragati S et al. Recent advances in periodontal drug
delivery systems. International Journal of Drug Delivery
1(2009) 1-14
 K. Schwach-Abdellaoui et al. Local delivery of
antimicrobial agents for the treatment of periodontal
diseases. European Journal of Pharmaceutics and
Biopharmaceutics 50 (2000) 83-99
77

78.  RAMS & SLOTS. Local delivery of
antimicrobial agents in the periodontal
pocket. Perio 2000, Vol. 10, 1996, 139-159
 Internet sources.
78