the seminar explains local drug delivery in periodontics.

1. S
LOCAL DRUG DELIVERY

2. Contents
• Introduction
• Systemic antibiotics vs. local drug delivery
• Principle of local drug delivery
• Goal of local drug delivery
• Ideal requirements
• Indications, Contra-indications
• Advantages, Disadvantages
• Classification
• Different physical forms
• Factors affecting local drug delivery in periodontal pocket
2

3. • Non sustained pocket delivery
• Sustained release drug delivery.
• Controlled release delivery agents
• Commonly used drugs LDD
•Other Drugs
• Future trends
• Conclusion
3

4. INTRODUCTION
• Periodontal disease is a multifactorial disease where putative
periodontopathogens trigger chronic inflammatory and immune responses
•Usually the host response resolves the infection without pathosis , but if the host-
parasite equilibrium is lost, it results in destruction of the tissues
(Rabbani GM,Ash MM, Caffesse RG .The effectiveness of subgingival scaling and root plaining in calculus removal. J Periodontal 1981;Volume 52;Number 3.119-
123)
• Mechanical therapy has always been the first line of therapy
4

5. LIMITATIONS OF MECHANICAL THERAPY
• Intra-oral translocation of perio-pathogens.
• Invasion into tissues from other intraoral niches such as the tongue, tonsils,
and the mucous membranes.
• Invasion into dentinal tubules
• Bacterial regrowth and recolonization of the pocket occur, with subgingival
bacterial counts being restored almost to pre-treatment values 3 to 7 days
after treatment
Harper DS, Robinson PJ. Correlation of histometric, microbial, and clinical indicators of periodontal disease status before and after root planning. J Clin
Periodontol 1987; 14:190-196
Quirynen M, De Soete M, Dierickx K, van Steenberghe D: The intra-oral translocation of periodontopathogens jeopardises the outcome of periodontal
therapy. A review of the literature. J Clin Periodontol 2001; 28: 499-507.
5

6. Systemic antimicrobial therapy was advocated as an adjunct with
mechanical treatment to prevent recolonization of bacteria
Greenstein G, Polson A. The role of local drug delivery in the management of periodontal diseases: A comprehensive
review. J Periodontol 1998;69: 507-520
SYSTEMIC ANTIBIOTICS IN PERIODONTAL THERAPY
Side effects including hypersensitivity, gastrointestinal intolerance and the development
of bacterial resistance have been described.
Some studies also reported poor results due to
-inadequate concentration at the site of action
-inability to be retained locally for a sufficient period of time.
Goodson JM. Antimicrobial strategies for treatment of periodontal diseases. Periodontol 2000.1994;5:142-68
Walker CB. The acquisition of antibiotic resistance in the periodontal flora. Periodontol 2000.1996;10:78-88. 6

7. LOCAL DRUG DELIVERY
• To overcome the undesirable effects, several local drug delivery systems have been
developed.
- It was first proposed by Goodson et al in 1979. He used tetracycline in hollow
fibres
Goodson J.M.,Haffajee A.,S. S. Socransky:Periodontal therapy by local delivery of tetracycline J Clin Periodontol
1979; 6: 83-92
7

8. Stoller et al (1998) studied doxycycline hyclate
GOODSON et al 1979 - used hollow tetracycline fibres
D. Steinberg et al (1990) researched chlorhexidine as a LDD
Nakagawa T et al (1991) used minocycline
Ainamo et al (1992) studied 25% metronidazole gel
HISTORY
8

9. Systemic vs local
ISSUE SYSTEMIC LOCAL
Drug distribution Wide distribution Narrow effect range
Drug concentration Variable levels in different body
components
high dose at treated sites
low levels elsewhere
Therapeutic potential May reach widely
distribution is better
May act better locally on biofilm
bacteria
Problems Systemic side effects reinfection at the treated sites
Diagnostic problems Identification of pathogens ,
choice of drug
Distribution pattern of pathogens
and lesions , identification of sites
to be treated.
Lindhe 4th edition , the use of antibiotics in periodontal therapy; 496-498 ) 9

10. Lindhe 4th edition , the use of antibiotics in periodontal therapy; 496-498
10

11. TERMINOLOGY
LOCAL DRUG DELIVERY/ SITE-SPECIFIC DELIVERY
• The terms "local delivery" and "site-specific delivery" are sometimes
used synonymously.
• A local delivery device consists of a drug reservoir and a limiting
element that controls the rate of medicament release.
Position paper: The role of controlled drug delivery for periodontitis. J Periodontol 2000; 71:125-140.
Sachin Sinha Role of local drug delivery in periodontics: A review.Journal of Research and Advancement in
Dentistry July- Oct 2012, Vol.1 No. 3,
11

12. DELIVERY
SYSTEMS
Controlled
delivery
systems
Sustained
release
1. less than 24 hours.
2. 2 to 4 applications.
3. may last weeks to months.
4. commonly referred to as
sustained-release, prolonged-
release, slow release, sustained-
action, prolonged-action or
extended-action.
1. exceeds 1 day
2. may need to be
administered only once.
3. Follow zero order kinetics.
4. commonly referred to as
timed-release, controlled-
release 12

13. First order and zero order kinetics
www.pharmainfo.net/og/rcp/downloads 13

14. SCIENTIFIC RATIONALE
• The scientific rationale for local drug delivery in periodontal pockets was
to kill and inhibit the sub gingival bacteria that are not accessible or
eliminated by hand or power driven instruments
[ Aubrey Soskolni W. Sub gingival delivery of therapeutic agents in the treatment of periodontal diseases. Crit. Res. Oral
Bio Med1997; 8(2):164-174]. 14

15. GOAL OF LOCAL DRUG DELIVERY
The primary goal in using an intra pocket device for the delivery of an
antibacterial agent is the achievement and maintenance of therapeutic
levels of the drug for the required period of time. This inhibits or kills
the pathogens, without any harm to the tissues.
[Goodson JM. Controlled drug delivery:A new means of treatment of dental diseases. Compend Cont Educ Dent
1985;6:27-36]
15

16. PRINCIPLE SITE FOR LOCAL DRUG DELIVERY
The Periodontal Pocket
1. Natural reservoir
2. Easily accessible for insertion of devices
3. GCF is a leaching medium or drug release
4. Gets distributed from pocket
Thus, the periodontal pocket is a natural site for treatment with local
release delivery system.
16
[ Aubrey Soskolni W. Sub gingival delivery of therapeutic agents in the treatment of periodontal diseases. Crit. Res. Oral
Bio Med1997; 8(2):164-174].

17. Ideal requisites of locally delivered drug
specific for periodontal pathogens
Drug must show in-vitro activity against the organisms
Target dose sufficient to kill the target organism should not have adverse effects
Substantivity
Prolonged shelf life
Biodegradable and Biocompatible
Ease of placement
Ready to use chairside
Should be economical
. Slots J, Rams TE. Local delivery of antimicrobial
agents in the periodontal pocket. Periodontol
2000 1996; Vol. 10: 139-59.
Goodson JM, Hogan PE, Dunham SL. Clinical
responses following periodontal treatment by
local drug delivery. J Periodontol; 1985 Special
Issue: 81 - 87. 17

18. INDICATIONS
1. As an adjunct to scaling and root planing
2. Periodontal maintenance therapy and in shallow and residual
pockets post successful phase I therapy
3. For whom surgery is contraindicated or those who refuse surgical
treatment
Rose LF, Mealey BL, Genco RJ, Cohen DW. Periodontics. China: Elsevier Mosby; 2004
Magnusson I, Lindhe J. et al Recolonisation of a subgingival microbiota following scaling in deep pockets. J Clin
Periodontal 1984:11;193-207 18

19. CONTRAINDICATIONS
1. Therapies other than LDDs should be considered when:
• Multiple sites with PD greater than 5 mm exist in the same
Quadrant.
• The use of LDAs has failed to control periodontitis (e.g. reduction of
PD).
• Presence of intra-bony defects)American Academy of Periodontology Statement on Local Delivery of Sustained or Controlled Release Antimicrobials
as Adjunctive Therapy in the Treatment of Periodontitis.J Periodontal 2006; Volume 77, Number 8
19

20. CONTRAINDICATIONS
2. Periodontal patients with known hypersensitivity reaction to any of
the antimicrobials for periodontal therapy.
3. In pregnant or lactating patients
4. Patients susceptible to infective endocarditis to avoid the risk of
bacteremia.
Rose LF, Mealey BL, Genco RJ, Cohen DW. Periodontics. China: Elsevier Mosby; 2004
Magnusson I, Lindhe J. et al Recolonisation of a subgingival microbiota following scaling in deep pockets. J Clin
Periodontal 1984:11;193-207
(Divya P.V, K. Nandakumar. Local drug delivery-Periocol in periodontics. Trends Biomater. Artif. Organs. 2006: 19: 7408020

21. 1. Attains a 100- fold higher concentration of anti microbial agent in sub-gingival sites
2. Reduces patient dose by over 400 fold thereby reducing chances of drug resistance
and side effects caused by systemic antibiotics
3. Small doses can be administered.
4. Maintain contact with the pathogens in the infected site.
5. Can employ broad spectrum antiseptics like CHX which cannot be given systemically.
6. Super-infection and drug resistance are rare.
Rams TE, Slots J. Local delivery of antimicrobial agents in the periodontal pocket. Periodontol 2000, 1996; 10: 139159.
21
ADVANTAGES

22. DISADVANTAGES
1. Patient may not comply to placement of the drug subgingivally.
2. Does not have any effect on adjacent or nearby structures such as
tonsils, buccal mucosa etc so may cause chances of re-infection.
3. Time consuming
4. Costly
5. In presence of generalised pockets, other periodontal therapies
should be used.
6. Difficulty in placing the device at the base of the pocket.
Rams TE, Slots J. Local delivery of antimicrobial agents in the periodontal pocket. Periodontol 2000, 1996; 10: 139159.
22

23. I. Langer and Peppas (1981) - Based on their mechanism of action
II. Kornman (1993) - Reservoirs with/without a Rate Controlling System
III. Rams And Slots, 1996 - Based On application of Therapy
IV. Soskolne WA, 1997 - Based on Dosage Form
V. Greenstein & Tonetti, 2000 - Based On Duration of Action
VI. Soskolone WA , 2004 - Biodegradable devices , Non-degradable devices
23
CLASSIFICATIONS

24. CLASSIFICATIONS
I. Langer and Peppas (1981)
Classified controlled drug release polymeric systems based on their mechanism of action..
1. Diffusion Controlled Systems
a) Matrices (monolithic devices
b) Reservoirs (membrane devices)
2. Chemically Controlled Systems
a) Erodible systems (biodegradable)
b) Pendant chain systems
3. Solvent Activated Systems
a) Osmotic systems
b) Swelling controlled systems
4. Release Induced By External Forces (magnetic)
Langer R, Peppas N. Present and future applications of biomaterials in controlled drug delivery systems. Biomaterials
1981; 2: 201-214.
24

25. II. Kornman (1993) has Classified the Controlled Release Local Delivery
System as
1. Reservoirs without a Rate Controlling System like hollow fibers, gels and
dialysis tubing. (hollow fibres, dialysis tubing, gel)
2. Reservoirs with a Rate Controlling System like Erodible Polymeric
matrices, Microporous polymer membrane, Monolithic matrices and
coated drug particles.(monolithic fibres, acrylic strips, ethyl cellulose
strips,EVA fibres)
Kornman KS. Controlled-Release Local Delivery Antimicrobials in Periodontics: Prospects for the Future. J
Periodontol. 1993; 64: 782-791. 25

26. III. Rams And Slots, 1996: Based On application of Therapy
1) Personally Applied (patient home self-care)
A. Non-sustained subgingival drug delivery (home oral irrigation)
B. Sustained subgingival drug delivery (none developed to date)
2) Professionally Applied (in dental office)
A. Non-sustained subgingival drug delivery (professional pocket irrigation)
B. Sustained subgingival drug delivery (controlled release device)
Rams TE, Slots J. Local delivery of antimicrobial agents in the periodontal pockets. Periodontology 2000
1996;10:139-159.
26

27. IV. Soskolne WA, 1997: Based on Dosage form
Devices have been developed in three broad dosage forms:
a. Fibers e.g. Tetracycline
b. Films/ slabs e.g. Chlorhexidine chip
1. Non-degradable films 2. Degradable devices
c. Injectable systems e.g. Minocycline
Soskolne WA, Heasman PA, Stabholz A, et al. Sustained local delivery of Chlorhexidine in the treatment of
Periodontitis: a multicenter study. J Periodontol 1997;68:32-38.
27

28. V. Greenstein & Tonetti, 2000 Based On Duration of Action
According to the duration of drug release, the local delivery devices
used in periodontology can be divided into two classes:
A. Sustained Release Devices
• Drug delivery for less than 24 hrs
• Require multiple applications • Follow first order kinetics
B. Controlled Release Devices
• Duration of drug release exceeds 24 hrs or for atleast 3 days
following application e.g. 5% clindamycin in Eudragit
Greenstein G, Tonetti M. Academy report: The role of controlled drug delivery for periodontitis (Position paper). J.
Periodontol. 2000; 71: 125-140.
28

29. VI. Soskolone WA, Friedman M. Intra pocket devices can be divided
in two broad categories
Depending on degradability:
1. Non-degradable devices (first generation)
2. Biodegradable devices (second generation)
Soskolone WA, Friedman M. Intra-periodontal Pocket Drug Delivery Systems. Ed By Michael J Rathbone., In:
Oral Mucosal Drug Delivery 2004; 74, Marcel Dekker Inc; 359- 79. 29

30. Factors Affecting Local Delivery of Agents in Periodontal Pockets
(Goodson 1979)
The most important factors that affect the local delivery of
agents to the periodontal pocket are
1. Subgingival drug- microbial contact
2. Effective subgingival drug concentration.
3. Time.
4. Substantivity.
30

31. Sub-gingival drug microbial contact
• An adequate drug-microbial contact time must be attained for an
antimicrobial agent to exert its bactericidal or bacteriostatic effects
against targeted microorganisms. Gingival crevicular fluid flow into
• Periodontal pockets averages 20 чl per hour and markedly increases
with tissue inflammation.
• Hence, inflammation needs to be controlled prior the use of LDDs.
Rams TE, Slots J. Local delivery of antimicrobial agents in the periodontal pockets. Periodontology 2000
1996;10:139-159. 31

32. Effective Subgingival Concentration
• Drug should have a dose higher than Minimal Inhibitory
Concentration (MIC).
• Antimicrobial agents that exert bactericidal effects within a 5-minute
time period are preferable for sub- gingival irrigation.
Rams TE, Slots J. Local delivery of antimicrobial agents in the periodontal pockets. Periodontology 2000
1996;10:139-159.
32

33. 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.
• Drug kinetics should follow zero order to stay there for long
time
Rams TE, Slots J. Local delivery of antimicrobial agents in the periodontal pockets. Periodontology 2000
1996;10:139-159.
33

34. SUBSTANTIVITY
• Substantivity refers to property of a substance to bind to soft and/ or
hard tissue of the pocket, thereby establishing a drug reservoir.
• Incorporation of drug into various vehicles or devices, prior to
placement into periodontal pocket enhances substantively.
Influenced by a series of parameters like:
• Concentration of the medication
• Length of time of contact of the solution with the oral structures
• pH
• Temperature
Goodson J. Pharmacokinetic principles controlling efficacy of oral therapy. J Dent Res 1989;68: 1625- 32.
Greenstein G,Tonetti M.Academy report: The role of controlled drug delivery for periodontitis(Position paper).J
Periodontol 2000;71:125-40. 34

35. Design of local periodontal delivery systems
• Once an intrinsically efficacious drug is selected the design of
its local periodontal delivery device requires the definition of
several objectives.
• As a general rule dosage regimens to treat biofilm based
infections aim at obtaining a profile able to maximise the area
under the concentration curve; i.e obtaining high concentrations
for longer durations.
35

36. • The intracrevicular delivery devices should be loaded with a drug reservoir of
sufficient size to satisfy the concentration and time objectives.
• The same antimicrobial is available in different chemical forms with different
solubility profiles;
• The selected antibiotic may in itself impose limitations on the choice of carrier
(resorbable or non resorbable)
36

37. Vehicles
• Solutions
• Paste
• Hollow fibres
• Acrylic strips
• Monolithic fibres
• Resorbable cellulose
• Collagen
• Biodegradable gel.
37

38. INJECTABLE
SYSTEMS
Easy &
effective
Cost saving
STRIPS &
COMPACTS
Polymers and
monomers
impregnated
with drug
Metronidazol
e CHX,
Augmentin,
Tetracycline,
Doxycycline
VESICULAR
SYSTEMS
Mimic
biomembra
nes
Triclosan.,
CHX
MICROPARTI
CLE SYSTEM
Biodegradabl
e PLA or
PGLA
Tetracycline
& doxycycline
microspheres
NANOPARTIC
ULATE
SYSTEM
Targeted
controlled
slow drug
release
Bioadhesive
& increases
stability
FIBRES
Hollow
Monofilament
Tetracycline
Chlorhexidine
FILMS
Matrix delivery
systems
Biodegradable –
Soluble films
Fish collagen
Dissolution
Steinberg et al
Non
biodegradable –
Insoluble films
Ethyl cellulose
diffusion
CHX,
tetracyclines,
metronidazole
GELS
Solid/semisoli
d
formulations
Base –
Methyl
cellulose
CHX,
metronidazol
e, tetracycline
etc
38
VARIOUS DELIVERY SYSTEMS USED

39. STRIPS &
COMPACTS
Polymers and
monomers
impregnated with
drug
Metronidazole
CHX, Augmentin,
Tetracycline,
Doxycycline
VESICULAR
SYSTEMS
Mimic
biomembranes
Triclosan., CHX
MICROPARTICLE
SYSTEM
Biodegradable PLA
or PGLA
Tetracycline &
doxycycline
microspheres
NANOPARTICULATE
SYSTEM
Targeted controlled
slow drug release
Bioadhesive &
increases stability
39

40. COMPARISON OF DRUG DELIVERY SYSTEMS
FOR THE MANAGEMENT OF
PERIODONTITIS
40

41. DRUG SELECTION
• Identification of periodontal pathogens
• Is advisable to do bacterial culture and sensitivity testing - Magnusson 1989
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
• No single drug is the universal drug of choice.
41

42. VARIOUS DRUGS/AGENTS USED IN THE LOCAL DRUG
DELIVERY SYSTEMS
1. TETRACYCLINE
2. DOXYCYCLINE
3. MINOCYCLINE
4. METRONIDAZOLE
5. CHLORHEXIDINE
6. OTHER DRUGS LIKE CLARITHROMYCIN, ALENDRONATES,
OFLOXACIN, CLINDAMYCIN and other newer drug delivery systems.
42

43. TETRACYCLINE
• Broad spectrum antibiotics with activity against both gram positive and gram
negative organisms.
• Bacteriostatic agents but may have a bactericidal effects in high concentrations
(Walker 1996). These drugs principally acts by inhibiting protein synthesis
• Goodson’s first delivery devices involved hollow fibres of cellulose acetate filled with
tetracycline in 1979.
• 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
43

44. VARIOUS DRUGS USED AS CONTROLLED RELEASED
SYSTEMS
TETRACYCLINE :
• 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
44

45. • In addition to its antibacterial action, it also possess the following function:
•Demineralizes dentin cementum and dentin, when applied topically
•Enhancing attachment of fibroblasts to the tooth surface
(Wikesjo et al 1986; Morrison et al 1992)
45

46. • Has high substantivity i.e. after local delivery, it has been detected
at 1-20µm within epithelial tissues
(Ciancio et al 1992)
• Detectable in high concentrations GCF several weeks following
application
(Wikesjo et al 1986)
• Collagenase inhibition, anti-bone resorption effect, anti-
inflammatory actions
46
ADVANTAGES

47. DISADVANTAGES
1. Development of antibiotic resistance
2. Ability to kill benign organisms associated with health as well as
pathogens.
Lacroix JM, Walker CB. Detection and incidence of the tetracycline resistant determinanttet (m) in the microflora associated with
adult periodontitis. J Periodontol 1995;66(2):102 108.
47

48. TETRACYCLINE LDD SYSTEMS
tetracycline
Tetracuycline
fibres
Tetracycline
gel
Tetracycline
films
48

49. 1. TETRACYCLINE GEL
The purpose was to reduce the polymer concentration and to obtain
reasonable viscosity at a lower concentration of pluronic acid.
A 20% wt/wt pluronic gel - Tetracycline Serratiopeptidase Containing
Periodontal Gel Formulation
2. TETRACYCLINE FILMS
Atelocollagen films with immobilized tetracycline have been found to
produce an effective MIC dose in the gingival crevicular fluid for up
to 10 days.
[M. Minabe, A. Uematsu, K. Nishijima, E. Tomomatsu, T. Tamura,T. Hori, T. Umemoto, T. Hino, Application of a local drug delivery
system to periodontal therapy. Development of collagen preparations with immobilized tetracycline, J.Periodontol. 60 (1989)
113± 117
Maheshwari M, Miglani G, Mali A, Paradkar A, Yamamura S, Kadam S. Development of Tetracycline Serratiopeptidase
Containing Periodontal Gel: Formulation and Preliminary Clinical Study; AAPS Pharm Sci Tech 2006; 7 (3) Article 76:E162-
171.
49

50. SERUM AND GCF CONCENTRATION OF
COMMONLY USED ANTIBIOTICS
50

51. PERIOCOL TC
The first generation non-degradable devices have been replaced by the
second-generation degradable devices .
• PerioCol -TC vial contains Type1, fibrillar collagen of fish origin of
approximately 25 mg, impregnated with approx. 2.0mg of Tetracycline
Hydrochloride IP, sterilized by gamma irradiation.
- releases tetracycline invitro for a period of 8 to 12 days.
- biocompatible and absolutely safe for human applications
PerioCol-TC should not be used in any Patient with a known sensitivity to
Tetracycline Hydrochloride and Collagen. Not recommended in acutely
abscessed periodontal pocket
51

52. TYPES OF FIBRES
• MONLITHIC
• HOLLOW
• RESORBABLE
52

53. TETRACYCLINE fibres (ACTISITE)
• They 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 fibre is flexible
and can be folded on itself to nearly fill the pocket
• Able to release and maintain tetracycline 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 fibres provide bactericidal concentration of
tetracycline.
53

54. TECHNIQUE
• An individual or several teeth can be treated at a time
• Short lengths of fibre, 2-3 inches are taken in a cotton
forceps and placed at the opening of the pocket to be
treated
• The fibre folded on itself
• The folding procedure might be repeated until all the
pockets are nearly filled
54

55. • 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)
• Fibres should be in place for 7-14 days
• Fibre removal (in case of non-resorbable fibres) is fairly
simple. They can be teased out of the pockets with a curette
55

56. .
2-3 inches
placed at the opening
of the pocket to be
treated- isolation is
required
Folded inside –
buccal, lingual,
interproximally.
DROP OF TISSUE
ADHESIVE
7-14 days later ,
removed with
curette
PACK can be
placed56

57. INSTRUCTIONS TO BE GIVEN TO THE
PATIENT
• Not to brush or floss the treated areas until fibres are
removed
• To rinse with chlorhexidine mouth rinse while the fibres
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 fibre removal (in case of
non-resorbable fibres)
• To come for recall visit at 4-6 weeks 57

58. 58

59. Review of Literature
Goodson et al (1979) showed the virtual elimination of spirochetes from the gingival
sulcus is possible by a single placement of tetracycline-filled hollow fibers local Drug
Delivery and spirochetes, once eliminated from a site, do not rapidly re-colonise
despite the persistence of viable organisms elsewhere in the mouth.
Goodson et al (1985) compared the hollow fibres versus monolithic ethyl vinyl
acetate. Monolithic fibre loaded with 25% tetracycline provided sustained release for
10 days. The average intrasulcular tetracycline concentration measured at the end of
10 day period was 643 ug/ml. At these sites, total counts of spirochetes, motile rods
and nonmotile rods were significantly reduced immediately following treatment.
59

60. • .
Mombelli et al (2001) concluded that therapy of peri-implantitis by local delivery
of tetracycline had a positive effect on clinical and microbiological parameters
Rushin K et al (2016) discussed the management of an intra-bony defect with
locally delivered teracycline fibres and splinting on a root canal treated tooth. The
outcome of this case highlights a cost effective regenerative technique, without
using bone grafts and GTR membranes, and also the importance of stabilization of
a tooth during its healing phase post surgically for increasing its prognosis.
60

61. 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)
61

62. 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
• 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 62

63. TECHNIQUE
• Liquid delivery system containing 10% doxycycline
hyclate is contained within a syringe that has a blunt
ended 23 gauge cannula attached. The cannula has a
diameter of a periodontal probe
• The tip of the cannula is introduced to the depth of the
pocket and the drug is expressed out
63

64. • As it begins to harden on contact with the moisture and
during the 1-2 minutes of hardening, it is packed into
the pocket using the underside of the moistened curette
or other blunt-ended instrument
• Immediately after administration, the polymer slightly
protrudes from the pocket orifice
• Periodontal dressing or adhesive is used as an aid in
retention of the system
• Instructions given to the patient is in lieu with
tetracycline fibres
64

65. 65

66. MINOCYCLINE
• Minocycline HCl, a semi synthetic tetracycline is one of the most active antibiotics
for microorganisms associated with periodontitis. Its chemical formula is
C23H27N3O7
• Minocycline has significant antimicrobial activity against a wide range of
organisms as well as an anticollagenase effect.
Dollery, C. Therapeutic Drugs. Churchill Livingstone, USA, 1999, Vol. 2, pp. M187-M188
Maehara R, Hinode D, Terai H, Sato M, Nakamura R, Matsuda N, et al. Inhibition of bacterial and mammalian collagenolytic activities by tetracyclines. Nippon Shishubyo Gakkai Kaishi 1998;30:182-90
66

67. RATIONALE BEHIND THE USE OF MINOCYCLINE IN
PERIODONTAL DISEASES
Sweetman, S.C. Martindale: the complete drug reference. 33rd ed., Pharmaceutical Press, London, 2009.
[Academy report: The role of controlled drug delivery for periodontitis. J. Periodontol., 2000, 71, 125-140.].
1. Broad spectrum of activity: bacteriostatic at low concentrations and bactericidal at high
concentrations.
2.Property of substantivity i.e. ability to bind to the soft and hard tissue walls of the pocket
thereby establishing a drug reservoir.
67

68. [Geng, S.; Cao, C.; Chen, Z. The effect of non-surgical periodontal and adjunctive minocycline-HCL treatments on collagenase activity. Zhonghua Kou Qiang Yi Xue Za Zhi.,
2000, 35, 336-339.].
[Dollery, C. Therapeutic Drugs. Churchill Livingstone, USA, 1999, Vol. 2, pp. M187-M188
[Babich, H.; Tipton, D.A. In vitro response of human gingival epithelioid S-G cells to minocycline. Toxicol. In Vitro, 2002, 16, 1121.].
3. Anti-collagenase activity against P.gingivalis, human gingival fibroblasts associated
with induction of inflammation.
4. Higher lipid solubility ensures rapid passage through the lipid bilayer of the
bacterial cell wall and inhibits protein synthesis.
5. Ability to enhance the activity of gingival epithelial cells to participate in the early
inflammatory phase of periodontal wound healing.
68

69. 6. Lastly it is seen that uptake of minocycline via different transport systems in human
gingival fibroblasts helps attaining higher levels in gingival cervicular fluid than blood, thus
enhancing the effectiveness of the minocycline against invasive pathogens involved in
periodontal diseases.
Yang, Q.; Nakkula, R.J.; Walters, J.D. Accumulation of ciprofloxacin and minocycline by cultured human gingival fibroblasts. J. Dent. Res., 2002, 81, 836-840
.Brayton, J.J.; Yang, Q.; Nakkula, R.J.; Walters, J.D. An in vitro model of ciprofloxacin and minocycline transport by oral epithilial cells. J. Periodontol., 2002, 73, 1267-1272.)
69

70. MINOCYCLINE
(DENTOMYCINE AND PERIOCLINE)
• 3 modes of local application are available:
•Film
•Microspheres
•Ointment
It is a bacteriostatic
70

71. Film
• Ethylcellulose containing 30% of minocycline cast
from ethanol, chloroform or chloroform with
polyethylene glycol were tested as 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
71

72. Microspheres:
• Minocycline micro-encapsulated in a resorbable poly glycolide-lactide
slow release polymer 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
(Braswell et al)
72

73. Microspheres :
Injected into the pocket
Adhered to the soft tissue
Dissolves
Releases minocycline in sustained manner
73

74. • Once in the pocket the micospheres react with the crevicular fluid which
hydrolyzes the polymer causing water-filled channels to form inside the
microspheres
• These holes become the pathway for the antibiotic for sustained release
• The minocycline then diffuses through these portals and permeates the
surrounding tissues
• Over a period of time, the microspheres themselves get fragmented through
polymer hydrolysis and degrade and are ultimately bioresorbed.
• It is reported that the microspheres are completely biodegraded in about 21
days
74

75. Ointment:
•It is a light yellow colour 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 application per
week for 4 weeks, 2 applications at intervals of 1 or 2 weeks,
3 applications at 2 weekly intervals were effective
75

76. 76

77. REVIEW OF LITERATURE
Nakagawa T et al (1991) revealed that Periocline effectively eliminated periodontopathic gram-
negative bacteria. These results indicated that a combination of Scaling and Root Planing with local
administration of 2% minocycline for recurrent periodontal pockets brought about more satisfactory
results than conventional SRP.
Van Steenberghe D et al (1999) compared SRP and subgingival minocycline ointment for 15 months
and found subgingival administration of minocycline ointment in the treatment of adult periodontitis
is safe and leads to significant adjunctive improvement after subgingival instrumentation in both
clinical and microbiologic variables over a 15-month period
77

78. • Hellström M.K et al (2008) conducted a study to evaluate the effects of minocycline microspheres on
periodontal probing depth reduction when used in combination with surgery in adults with moderate to
severe, chronic periodontitis. applications of local minocycline as an adjunct to surgery in adults with
moderate to severe, chronic periodontitis were associated with statistically significant greater reductions in
probing depth than surgery alone.
78

79. • Ruan H et al (2016) formulated a thermoresponsive gel for minocycline (MCL) with chitosan/β-glycerophosphate.
The final preparations contained 0.5% (w/v) chitosan, 1.8% (w/v) β-GP and 2% (w/v) MCL. The constituents of the
in situ gels formulation had a well-sustained release efficacy on the animal model of periodontitis
79

80. • Thus, minocycline can be used as a adjunct to
mechanical debridement with improved
effectiveness for treatment of chronic periodontitis
Vanderkerckhove et al
80

81. 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 and it is found to eliminate spirochetes from
ANUG lesions.
(Brit and Prohlod 1986)
81

82. METRONIDAZOLE DENTAL GEL (ELYZOL)
• Resorbable
• Consists of 25% of Metronidazole benzoate in a matrix consisting of
Glyceryl mono-oleate
Sesame oil
• The gel is subgingivally placed with a syringe and a blunt cannula. The drug
concentration in crevicular fluid follows an exponential pattern which is
compatible with sustained drug delivery
82

83. 83

84. 84

85. REVIEW OF LITERATURE
Ainamo et al (1992) compared the effect of
metronidazole 25% gel with subgingival scaling in adult
Periodontitis and found that both periodontal pocket
depth and bleeding on probing were significantly
reduced in both groups.
Stelzel M et al (1997) compared topical application of a
metronidazole 25% dental gel with subgingival scaling
and found better results as compared to SRP alone .
85

86. Al Mubaraaak et al (2000) assessed the effect of topical application
of a metronidazole gel (ELYZOL DENTAL GEL), and adjunctive
therapy in the treatment of adult periodontitis clinically and found
that topical Elyzol treatment may improve periodontal health as
well as subgingival scaling and root planning therapy and adjunctive
treatment could obtain an additional therapeutic effect.
Paul Singh H et al (2016) studied the comparative effect of both aloe
vera gel and metronidazole gel and the results of both test groups
A.vera and metronidazole are comparable.Hence, local application
of Aloe vera can be an effective and affordable herbal substitute for
metronidazole
86

87. • 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)
87

88. 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)
88

89. CHLORHEXIDINE CHIP (PERIOCHIP)
• It is a bio-absorbable device
• Comprises of 34% Chlorhexidine in a cross-linked gelatin matrix
• Chip is 5 mm long, 4 mm wide with 2.5 mg of chlorhexidine gluconate
89

90. 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 fibres
90

91. 91

92. PERIOCOL- CG
• (PerioCol™-CG) is a controlled-release chlorhexidine chip. Each PerioColTM-CG contains
approximately 2.5 mg of chlorhexidine gluconate in a bio-degradeable matrix of Type 1
collagen derived from fish sources.
• It releases chlorhexidine in vitro with a release profile of approximately 40-45% within 24hrs
and afterward in linear fashion for 7-8 days. The release profile may be explained by initial
burst effect due to diffusion of the drug from the chip followed by release of the drug due to
enzymatic degradation
92

93. CHLOSITE
• Chlosite consists of 1.5% chlorhexidine bonded in a xanthan carrier substance. It contains
chlorhexidine in two different forms. The first form is 0.5 % highly soluble chlorhexidine
digluconate, also called chlorhexidine-bis (D-gluconate).
• This form of chlorhexidine is used as an antiseptic agent. The second form is a slow-release
1 % chlorhexidine dihydrochloride (a bis-biguanide with bacteriostatic characteristics).
• Chlosite uses xanthan gel as the carrier
• Xanthan in Chlosite provides good sub-gingival bonding of the local delivery device via
mucoadhesion, while the high Chlorhexidine content guarantees a safe bactericidal effect.
93

94. 94

95. REVIEW OF LITERATURE
D. Steinberg et al (1990): Release of Chlorhexidine from a degradable delivery
system and the degradation of the matrix is controlled by variation in the
formulation. This presented a new dental drug delivery system for sustained
release of chlorhexidine that can be used as an adjunct in the treatment of
periodontal diseases.
Jeffcoat M et al (1998) proved the efficacy of a controlled-release biodegradable
Chlorhexidine (CHX) (2.5 mg) chip when used as an adjunct to scaling and root
planing significantly reduced probing depth (PD) and improved clinical
attachment level (CAL) in adult periodontitis.
95

96. Paolantonio M et al (2008) provided further data supporting clinical and
microbiologic effects of Chlorhexidine chips when used as an adjunct to Scaling
and root planing.
They obtained significant reduction in Probing Depth (PD) and a clinical
attachment level (CAL) gain compared to SRP alone
Jose K et al (2016) evaluated the outcome of chlorhexidine chip and diode laser as
adjuncts to scaling and root planing and concluded Chlorhexidine local delivery
alone or in combination with diode laser decontamination is effective in reducing
PD and gaining CAL
96

97. Kaplish V, Walia M, Hari Kumar SL. Local drug delivery systems in the
treatment of periodontitis: A review. Pharmacophore 2013;4(2):39-49.
97

98. 98

99. 99

100. COMPARISON OF DRUGS USED FOR LOCAL
DELIVERY
100

101. OTHER DRUGS
101

102. 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
102

103. OFLOXACIN INSERTS (PT-01)
• PT-01 is a soluble insert, with both fast and sustained release parts containing 10%
ofloxacin and showed a constant drug level of above 2 mg/ml, (minimum MIC for most
pathogenic organisms) which could be sustained for up to 7 days
• The controlled release system exhibited a biphasic pattern with a rapid early release phase
peaking 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)
• Four weekly applications of the insert resulted in significant resolution of periodontal
inflammation and improvement in other clinical parameters compared to controls.
(Yamagami et al 1992)
103

104. ANTIBIOTIC RESISTANCE ASSOCIATED WITH
LOCAL DRUG DELIVERY SYSTEMS
• Local drug delivery provides a high drug concentration
at a specific site
• 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
104

105. • Exposure to sub inhibitory concentrations of metronidazole or minocycline
resulted in development of resistance among
P.gingivalis
P.intermedia
F.Nucleatum
P.Anaerobius
Walker et al, Larsen et al
• This suggests that repeated use of these agents can result in increased levels of
drug resistant bacteria
105

106. • 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)
106

107. LDD VS SRP
107

108. • Hanes et al. in their systematic review, stated that as compared to
SRP alone, when SRP is combined with certain local drug delivery
agents, statistically significant adjunctive effects on PD reduction or
CAL gain and decreased BOP were observed.
Hanes PJ, Purvis JP. Local anti-infective therapy: Pharmacological agents. A Systematic Review. Ann
Periodontal 2003;8:79-98
108

109. Future Trends in Local Drug Delivery
• The requirements for treating periodontal disease include a means for
targeting an anti infective agent to infection sites and sustaining its localized
concentration at effective levels for a sufficient time while concurrently
evoking minimal or no side effects. (Venkatesh A, Ramamurthy J 2012)
• Various newer agents are being investigated in the field of local drug
delivery to ensure maximum benefit.
Venkatesh, A. and Ramamurthy, J., 2012. Local drug delivery systems in the treatment of periodontitis–An
Overview. Int J Pharm Pharm Sci, 4(1), pp.30-37.
109

110. 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.
• At the end of 6 months, the mean GI, PI, SBI, PPD, CAL for the clarithromycin
group was significantly reduced. This product is still under investigation and yet
to be patented. (Agarwal E et al)
Agarwal, E., Pradeep, A.R., Bajaj, P. and Naik, S.B., 2012. Efficacy of local drug delivery of 0.5% clarithromycin gel as an
adjunct to non-surgical periodontal therapy in the treatment of current smokers with chronic periodontitis: a
randomized controlled clinical trial. Journal of periodontology, 83(9), pp.1155-1163. 110

111. Azithromycin Gel
• Pradeep AR (2013) evaluate the adjunctive effects of subgingivally
delivered 0.5% azithromycin as an adjunct to scaling and root planing
(SRP) in the treatment of chronic periodontitis in smokers.
• Significant improvement in clinical outcome were observed at 9 months.
Pradeep AR, Bajaj P, Agarwal E, Rao NS, Naik SB, Kalra N, Priyanka N. Local drug delivery of 0.5% azithromycin in
the treatment of chronic periodontitis among smokers. Aust Dent J 2013;58:34-40.
111

112. STATINS
• These agents are widely used to lower cholesterol.
• They also seem to modulate bone formation by increasing the expression of
BMP-2, inflammation and angiogenesis.
• Pradeep AR, Thorat MS (2010) investigated effectiveness of simvastatin(SMV)
1.2 mg gel into the periodontal pocket using a syringe with blunt cannula.
• Greater decrease in gingival index and PD and more CAL gain with significant
intrabony defect fill was observed.
Pradeep AR, Thorat MS. Clinical effect of subgingivally delivered simvastatin in the treatment of patients with chronic
periodontitis: A randomized clinical trial. J Periodontol 2010;81:214-22.
112

113. • Fajardo ME et al 2010 in their study shown that Atorvastatin have
beneficial effects on alveolar bone loss.
• Goes et al 2010 have shown that ATV was able to prevent alveolar bone
loss in rats.
• Pradeep AR et al (2013) observed significant increase in PD, CAL gain and
improved bone fill.
Pradeep AR, Kumari M, Rao NS, Martande SS, Naik S. Clinical efficacy of
subgingivally delivered 1.2% Atorvastatin in chronic periodontitis: A randomized
controlled clinical trial. J Periodontol 2013;84:871-9. 113

114. ALENDRONATE
• Increases alveolar bone density with systemic use and, has been found to
increase bone formation on local delivery into the periodontal pocket.
• The efficacy of 1% ALN gel used as an adjunct to SRP for the treatment of
intrabony defects in patients with chronic periodontitis with type 2 diabetes.
• Significant increase in the PD reduction, CAL gain, and improved bone fill
observed
Pradeep AR, Sharma A, Rao NS, Bajaj P, Naik SB, Kumari M.Local Drug Delivery of
Alendronate Gel for the Treatment of Patients With Chronic Periodontitis With Diabetes
Mellitus: A Double-Masked Controlled Clinical Trial. J Periodontol 2012;83:1322-1328.
114

115. METFORMIN
• Shown recently to stimulate osteoblasts and reduce alveolar bone loss.
• Efficacy of 0.5%, 1%, and 1.5% MF gel as a local drug delivery system in
adjunct to scaling and root planing for treatment of intrabony defects.
• Significant increase in the PD reduction, CAL gain, and improved IBD depth
reduction
Pradeep AR, Rao NS, Naik SB, Kumari M. Efficacy of Varying Concentrations
of Subgingivally Delivered Metformin in the Treatment of Chronic Periodontitis:
A Randomized Controlled Clinical Trial. J Periodontol 2013;84:212-220.
115

116. FIBROBLAST GROWTH FACTOR
• Very efficacious introduction in local drug delivery.
• To regenerate periodontal tissues, a sandwich membrane composed of a collagen
sponge scaffold and gelatin microspheres containing basic fibroblast growth factor
(bFGF) in a controlled-release system was developed.
• This sandwich membrane induced successful regeneration of the periodontal tissues
in a short period of time (4weeks ). (Nakahara T 2003)
Nakahara T, Nakamura T, Kobayashi E, Inoue M, Shigeno K et.al. Novel Approach to Regeneration of Periodontal
TissuesBased on in Situ.Tissue Engineering: Effects of Controlled Release of Basic Fibroblast Growth Factor from a
Sandwich Membrane. Tissue Engineering 2003, 9(1): 153-162.
116

117. NANOPARTICLES
• Owing to their small size, penetrate regions that may be inaccessible to other
delivery systems.
• These systems reduce the frequency of administration and further provide a
uniform distribution of the active agent over an extended period of time.
• Three preliminary studies have been conducted to assess the efficacy of
nanoparticles in periodontal drug delivery.
117

118. Chitosan Tripolyphosphate (TPP)
a) Dung et al used Antisense oligonucleotide- loaded (TPP) nanoparticles and
showed the sustained release of oligonucleotides which is suitable for the
local therapeutic application in periodontal diseases. (Pragati S 2009)
b) Pinon et al conducted a preliminary in vivo study in dogs with induced
periodontal defects using Triclosan-loaded polymeric (PLGA, PLA and
cellulose acetate phthalate) nanoparticles and suggested that triclosan-
loaded nanoparticles penetrate through the junctional epithelium. (Pragati S
2009)
Pragati S, Ashok S, Kuldeep S. Recent advances in periodontal drug delivery systems. Int J Drug Del 2009; 1: 1-14
Dung, D.T.K., Hai, T.H., Long, B.D. and Truc, P.N., 2009. Preparation and characterization of magnetic nanoparticles with
chitosan coating. In Journal of Physics: Conference Series (Vol. 187, No. 1, p. 012036). IOP Publishing.
.
118

119. HERBAL PRODUCTS
• Various herbal formulations like aloe vera, neem, tulsi, propolis, cocoa
husk, pomegranate, cranberry , etc. are being used widely these days.
(Kukreja BJ, Dodwad V 2012, Bansal S 2012)
• These products have shown promising results with no side effects and are
economical as well.
Kukreja BJ, Dodwad V. Herbal Mouthwashes – A Gift Of Nature: Int J Pharm Bio Sci 2012; 3: 46-52.
119

120. • The antimicrobial effects of green tea catechins on periodontopathogens
have been studied by Hirasawa et al (2002)
• They showed bactericidal activity against black pigmented organism at a
minimum inhibitory concentration (MIC) of 1 mg/ml
• Kudva P et al (2011) also demonstrated clinical and microbiological
improvements following the use of Green tea catechin chip as an adjunct
to scaling and root planing
Hirasawa, M., Takada, K., Makimura, M. and Otake, S., 2002. Improvement of periodontal status by green tea catechin
using a local delivery system: a clinical pilot study. Journal of periodontal research, 37(6), pp.433-438.
120

121. • The clinician’s decision to use LDAs should be based upon a
consideration of clinical findings, the patient’s dental and medical
history, scientific evidence, patient preferences, and advantages and
disadvantages of alternative therapies.
122

122. DISEASES THAT CAN BE TREATED WITH
LOCAL DRUG DELIVERY SYSTEMS
• All drugs were used to treat patients with chronic periodontitis
• Only tetracycline fibres and metronidazole were used to treat aggressive
periodontitis
• Mandell 1986 - Tetracycline fibers were not efficient in suppressing Aa – in J
P
• Mombelli et al (1997) - Tetracycline fibers were able to suppress, but not
eliminate Aa
• Riep et al (1996) -Local delivery of metronidazole too is not effective at
suppressing Aa levels 123

123. Thus, at present there is no concrete evidence to use
local delivery agents in the treatment of aggressive
periodontal diseases
124

124. 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 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
125

125. REMEMBER……..
• At present, there are insufficient data to indicate that one local drug delivery
service is clearly superior to all the other systems
• There is a lack of data to support the impression that local drug delivery in
conjunction with root planing reduces the need for periodontal surgery more
than scaling and root planing alone.
• Should not be substituted for oral hygiene procedures.
• Cigarette smoking has a negative influence on outcome of local drug therapy
(Kinane et al 1999)
126

126. FUTURE REQUIREMENTS
• Various drug delivery and drug targeting systems are
currently under development to obtain so that better and
effective administration of desired and newer drug can
be done through the best possible system
Increased dissolution velocity
Increased saturation solubility
Improved bioadhesivity and
Versatility in surface modification
• Long term longitudinal studies to be done to know the
durability of these drugs on long term basis
127

127. AAP consensus on LDD
• Thorough SRP is highly effective in the treatment of chronic
periodontitis and is the standard approach to non-surgical
periodontal therapy. Clinicians may consider the use of LDDs
in chronic periodontitis patients as an adjunct to SRP
128

128. REFERENCES
• (Rabbani GM,Ash MM, Caffesse RG .The effectiveness of subgingival scaling and root plaing in calculus
removal.J Periodontal 1981;Volume 52;Number 3.119-123)
• Quirynen M, De Soete M, Dierickx K, van Steenberghe D: The intra-oral translocation of
periodontopathogens jeopardises the outcome of periodontal therapy. A review of the literature. J Clin
Periodontol 2001; 28: 499-507.
• Harper DS, Robinson PJ. Correlation of histometric, microbial, and clinical indicators of periodontal
disease status before and after root planning. J Clin Periodontol 1987; 14:190-196
• Goodson JM. Antimicrobial strategies for treatment of periodontal diseases. Periodontol
2000.1994;5:142-68
• Walker CB. The acquisition of antibiotic resistance in the periodontal flora. Periodontol
2000.1996;10:78-88.
129

129. • Goodson J.M.,Haffajee A.,S. S. Socransky:Periodontal therapy by local delivery of tetracycline J Clin Periodontol
1979; 6: 83-92
• Prajapati J, Patel H, Agrawal YK. Targeted drug delivery for central nervous system: a review. Int J PharmPharm
Sci 2012; 4(3): 32-38
• Local drug delivery in periodontics: a strategic intervention. International journal of pharmacy and pharmaceutical
sciences. Vol 4, issue 4, 2012
• Local drug delivery in periodontal diseases. ……A review. NUJHS vol. 6, no.1, march 2016.
• Recent advances in periodontal drug delivery systems Pragati S, Ashok S., Kuldeep S. International Journal of Drug
Delivery 1(2009) 1-14
• Deeksha Joshi, Tarun Garg, Amit K. Goyal & Goutam Rath (2016) Advanced drug delivery approaches against
periodontitis, Drug Delivery, 23:2, 363-377
• Review: recent advances in periodontal formulations . mr. Prakash sapra, dr. Biraju D patel, dr. Dhaval V Patel, Dr.
Chetan H Borkhataria. International Journal of Pharmaceutical Chemistry and Analysis Vol.1, No.1, October 2014
130

130. • Local drug delivery system – A comprehensive review. Shaikh Samar,
Chaudhari Amit, Khadtare Yogesh Indian journal of applied research.
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• Carranza 11th edition
• Lindhe 5th edition
• Perio 2000. Vol. 10, 1996, 139-159
131

131. 132