Local drug delivery

1. LOCAL DRUG DELIVERY
GUIDEDBY ,
DR. AJEYBHAT
DR. SHILVANAANSARI
DR. RENJITHMADHAVAN
DR. SUNEETHIM DEY
SUBMITTEDBY ,
GANGAS NADARAJAN
180021975

2. CONTENTS
INTRODUCTION
LOCAL DRUG DELIVERY SYSTEM
 INTRODUCTION
 GOALS OF LOCAL DRUG DELIVERY
 HISTORY
 PRINCIPLES
 INDICATIONS
 CONTRAINDICATIONS
 CLASSIFICATIONS
 IDEAL REQUISITES
 ADVANTAGES
 DISADVANTAGES
 SUBSTANTIVITY
 COMPARISON OF DRUG DELIVERY FOR MANAGEMENT OF PERIODONTITIS .
 VEHICLES FOR LOCAL DRUG DELIVERY SYSTEMS

3. LOCAL DELIVERY DIVICES
 TETRACYCLINE FIBERS
 CHLORHEXIDINE BASED PRODUCTS
 SUBGINGIVAL DOXYCYCLINES
 SUBGINGIVAL MINOCYCLINES
 SUBGINGIVAL METRONIDASOLE
 SUBGINGIVAL MOXIFLOXACINE
FUTURE TRENDS
FUTURE REQUIREMENTS
CONCLUSION
REFFERENCE

4. INTRODUCTION
PERIODONTITIS
Periodontitis is defined as an inflammatory disease of supporting tissue of
teeth initiated by specific microorganism or group of specific microorganism ,
resulting in progressive destruction of the periodontium with periodontal
pocket formation , gingival recession , or combination of both .

5. • The traditional mechanical therapy alone is not sufficient for the treatment of
moderate to severe periodontitis with deeper pockets .
• To overcome this , local drug delivery into periodontal pocket is recommended .
• Systemic administration of medications results in local concentrations of free,
active drug in the periodontal pocket and surrounding tissues.

6. LOCAL DRUG DELIVERY SYSTEM
• Aim is targeting an anti infective agent to infection sites and sustaining its
localized concentration at effective levels for a sufficient time with minimal
or no side effects.
• 3 basic routes to localized adjunctive pharmacologic periodontic
therapy:
mouth rinses , subgingival irrigation and local delivery systems.

7. • Rinses are useful for supragingival biofilm control, modulation of gingival
Inflammation .
• They do not gain access to the subgingival environment .
• Irrigation solutions placed directly in to periodontal pockets
• A highly concentrated irrigating solution of a non substantive ( non binding) drug
becomes ineffective about 15 min following application

8. • This time can be prolonged by application of substantive drugs that bind to
the root surface and / or the soft tissue wall of the periodontal pocket and
establish a drug reservoir that can be slowly released .
• Goodson- in 1970s pointed out that successful pharmacologic
control of the periodontal microflora requires;
• Site
• Concentration
• Time

9. GOALS 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 the
therapeutic levels of the drug for the required period of time .
This inhibits or kills the pathogens , without any harm to the tissues .

10. HISTORY
GOODSON et al 1979 – Tetracycline fibers
D.STEINBERG et al 1990 – chlorhexidine as LDD
NAKAGAWA et al – 1991 – minocycline
Stoller et al 1998 – doxycycline hyclate
Ainamo et al 1992 -25% metronidazole gel

11. PRINCIPLES
The periodontal pocket
• Natural reservoir
• Easily accessible for insertion of devices
• GCF is the leaching medium
• Gets distributed from pockets

12. INDICATIONS
• In medically compromised patients where surgical procedures are not
recommended .
• Periodontal abscess .
• Periodontal maintenance therapy .
• Patient with GI intolerance to systemic drug medication .
• In failing implant cases .

13. CONTRAINDICATIONS
• In patients with history of allergy to a particular antimicrobial agent .
• In pregnancy and lactating periods .
• Children under the age of 12 years .
• Patient with complete renal failure .
• Patients susceptible to infective endocarditis .

14. CLASSIFICATIONOF LOCAL DRUG DELIVERY
(A) . Based on the application - Rams & slots ( 1996 )
• Personally applied
• Nonsustained subgingival drug delivery
• Home oral irrigation
• Traditional jet tips
• Oral irrigations
• Soft cone rubber tips ( pickpockets )
• Sustained local drug delivery .

15. Professionally applied in Dental office .
• Nonsustained subgingival drug delivery .
• Professional pocket irrigation .
• Sustained subgingival drug delivery .
• Controlled release devices
• Hollow fibers
• Dialysis tubing
• Strips
• Films

16. (B) . Based on the duration – Greenstein and Tonetti ( 2000)
• Sustained release device
• Device with drug delivery less than 24 h
• Require multiple applications .
• Follow first order drug kinetics
• Controlled release device
• Drug release more than 24 h
• Administration only once
• Follow zero order drug kinetics

17. (C) . Depending on degradability
• Non degradable devices ( First generation )
• Degradable devices ( Second generation )
(D) . Langer and peppas
• Diffusion controlled system
• Matrices
• Reservoirs
• Chemically controlled systems
• Pendant chain system
• Osmotic system
• Swelling controlled systems

18. (E) . Kornman classification of controlled release local drug delivery systems
Reservoirs without a rate controlling system Reservoirs with a rate controlling system
Eg : hollow fibers , gels Eg : Polymeric matrices

19. (F) . Depending on the origin .
• Allopathic / chemical
• Herbal / Ayurvedic
(G) . Based on the type of local drug delivery system
• Fibers
• Films
• Gels
• Strips
• Vesicular liposomal systems
• Microparticle systems
• Nanoparticle systems

20. IDEAL REQUISITES
• It should deliver drugs to the connective tissue apically and laterally of
the periodontal pockets .
• Maintain a microbiologically effective concentration .
• It should maintain the drug concentration in the periodontal pocket for
sufficient time .
• Easy to deliver into the pockets
• It should be biodegradable
• It should not develop bacterial resistance
• Minimal or no adverse effects
• It should not affect commensal microflora of pockets .

21. ADVANTAGES
• High concentration in subgingival sites .
• Independent of patient compliance .
• Does not harm the useful microflora of GI tract .
• Systemic intolerance is bypassed .
• Improved pharmacokinetics

22. DISADVANTAGES
• Difficulty in placing deeper sites .
• Has to be professionally placed .
• Complete drug penetration is not possible .
• Time consuming .

23. SUBSTANTIVITY
• It is refers to the property of a substance to bind to soft and / hard
tissue of the pockets , thereby establishing a drug reservoir .
• Incorporation of a drug into various vehicles or device , prior to
placement into periodontal pocket enhance sustantively .
• It is influenced by series of parameters like ;
 concentration of the meadium
 length of time of contact of the solution with the oral structures .
 Ph
 temperature

24. COMPARISON OF DRUG DELIVERY SYSTEM FOR THE
MANAGEMENT OF PERIODONTITIS
PHARMACO
KINETIC
VARIABLES
MOUTH
RINSE
SUBGINGIVAL
IRRIGATIONS
SYSTEMIC
DELIVERY
CONTROLLED
DELIVERY
SITE DELIVERY POOR GOOD GOOD GOOD
CONCENTRATION GOOD GOOD FAIR GOOD
DURATION POOR POOR FAIR GOOD

25. VEHICLES FOR LOCAL DELIVERY
Dentifrices
Mouthrinses
Chewing gum
Slow release devices

26. VARIOUS DRUGS / AGENTS USED
• TETRACYCLINE
• CHLORHEXIDINE
• DOXYCYCLINE
• MINOCYCLINE
• METRONIDAZOLE
• MOXIFLOXACINE
• OTHER DRUGS LIKE CLARITHROMYCIN , ALENDRONATES , OFLOXACIN ,
CLINDAMYCIN etc.

27. Tetracycline Containing Fibers
• The first local delivery product , was ethylene /vinyl acetate copolymer fiber
(diameter, 0.5 mm) that contained tetracycline(12.7 mg per 9 inches ) .
• Tolerated by oral tissues and for 10 days its sustained concentration
exceeding 1300 microgrms / ml
TETRACYCLINE BASED PRODUCTS
• GCF concentrations of only 4 to 8 µg/ml reported after systemic tetracycline
administration( 250mg 4 times daily for 10 days for total oral dose of 10 g)

28. • Tetracycline fibers reduces probing depth, bleeding on probing, and
periodontal pathogens and provided gains in clinical attachment level.
• These fibers are no longer commercially available.
• Disadvantages included time required for placement (≥ 10 min per tooth),
and a second patient appointment .
Placement of fibers around 12 or more teeth resulted in oral candidiasis in
few patients

29. PerioCol –TC is another tetracycline based product
• Each PerioCol- TC contains fish type 1 collagen (approximately 25 mg)
impregnated with approximately 2 mg of tetracycline hydrochloride
• PerioCol – TC releases tetracycline in vitro
for 8 to 10 days.
• A periodontal dressing should be placed to
avoid dislodging the fibers.
• Indicated for adult periodontitis with pocket
deeper than 5mm .
PerioCol - TC

30. • The fibers are moistened with saline and placed in to the periodontal pocket to a depth of the
pocket base; they are biodegradable
• PerioCol-TC is stored in a dry place between 5° C (41° F) and 25° C (77° F) and has a shelf life
of 2 years with proper storage.
Periodontal Plus AB
PERIODONTAL PLUS AB

31. • Periodontal Plus AB is a bioresorbable tetracycline fiber.
• It is 25 mg of pure fibrillar collagen evenly impregnated with approximately 2 mg of
tetracycline hydrochloride .
• Packed as a strip containing four individually packed and separable sterile product packs. The
fiber biodegrades in the periodontal pocket within 7 days.
• The fiber should be retained with a periodontal dressing or covered with a dental adhesive for
10 days.

32. CHLORHEXIDINE BASED PRODUCTS
• Chlorhexidine is active against a broad range of microbes.
• It disrupts the cell membrane and causes precipitation of the cytoplasm,
• resulting in cell death.
• The chip is stored at 20° to 25° C (68 to 77° F), with excursions permitted to 15° to 30°
C (59o to 86o F)
• The chlorhexidine chip is placed into the pocket directly from the foil container using
a forceps.

33. Subgingival Chlorhexidine in Chip Form
PerioChip
• PerioChip is a small chip (4.0 x 5.0 x 0.35 mm) that is composed of a
biodegradable hydrolyzed gelatin matrix.
• Cross linked with glutaraldehyde, and contains glycerin and water into
which 2.5 mg of chlorhexidine gluconate has been incorporated per chip.

34. • Maintains drug concentrations in the GCF more than 100 µg/mL for at least 7
days.
• Since the chip biodegrades within 7-10 days, a second appointment for
removal is not needed.
• Dental floss should be avoided for 10 days to avoid dislodging it.
PLACEMENT 0F PERIO CHIP

35. PerioCol-CG
• PerioCol-CG is a small, 10-mg chip (4 x 5 x 0.25-0.32 mm )designed as a collagen matrix
into which chlorhexidine gluconate (2.5 mg) is incorporated from a 20% chlorhexidine
solution .
PERIOCOL CG
• Resorb after 30 days but coronal edge will degrades within 10
days .
• It releases chlorhexidine at a rate of approximately 40% to
45% in the first 24 hours, followed by a linear release for 7 to 8
days

36. Subgingival Chlorhexidinein Gel Form
• Chlo-Site is a xanthan gel, consisting of a saccharide polymer as a three-dimensional mesh
containing 1.5% chlorhexidine in 0.5 mL of gel
• Individually packed for delivery in 0.25ml prefilled syringes fitted with a blunt side-exit
needle.
• The gel contains two types : a slow-release chlorhexidine digluconate (0.5%) and a rapid-
release chlorhexidine dihydrochloride (1.0%)

37. CHLORHEXIDINE GEL – CHLO SITE
• The gel disappear from the pocket in 10 to 30 days and chlorhexidine
concentration in GCF of more than 100 µg/ml for an average of 6-9 days.

38. Subgingival Chlorhexidinein Gel Form
• Chlo-Site is a xanthan gel, consisting of a saccharide polymer as a three-dimensional mesh
containing 1.5% chlorhexidine in 0.5 mL of gel
• Individually packed for delivery in 0.25ml prefilled syringes fitted with a blunt side-exit
needle.
• The gel contains two types : a slow-release chlorhexidine digluconate (0.5%) and a rapid-
release chlorhexidine dihydrochloride (1.0%)

39. DOXYCYCLINE BASED PRODUCTS
Doxycycline in gel form
A gel system involving the use of a syringe with 10%
doxycyclineAtridoxDoxycycline gel is a subgingival, controlled-release delivery
product composed of a two-syringe mixing system.

40. • Syringe A contains 450 mg of a bioabsorbable polymeric formulation of 36.7%
poly (D,L,-lactide) dissolved in 63.3% N-methyl-2-pyrrolidone
• Syringe B contains 50 mg of doxycycline hyclate,
equivalent to 42.5 mg of doxycycline.
Atridox two syringe system

41. • The two syringes are stored at 2° to 30° C (36° to 86° F).
• When mixed, the product is a viscous liquid of 500 mg, which contains 50 mg (10%) of
doxycycline hyclate . Indicated for the treatment of chronic adult periodontitis for a gain
in clinical attachment , reduction in probing depth and reduction of bleeding on
probing.
• Inhibit bacterial protein biosynthesis by interfering with transfer RNA(tRNA) and
messenger RNA(mRNA) at the ribosome Used by injecting the mixed contents of the
two syringes directly into the pocket
• The pocket contents are then covered with a periodontal dressing or a cyanoacrylate
dental adhesive.

42. • If not used immediately, the mixed contents in syringe A can be stored in an
airtight container at room temperature for a maximum of 3 days.
• The gel release doxycycline in the GCF over 7 days.
• The doxycycline gel is biodegradable and does not require removal.

44. LigosanSlow Release
• Resorbable doxycycline gel provided in a laminate pouch and stored under
refrigeration.
• It contains 1, 2, 4, 8, 10, or 16 single application cylinder cartridges, each
containing 260 mg of Ligosan Slow Release .

45. • Used by inserting the cartridge in to the caulking gun ,opening the spray
nozzle and then discharging the gel to the bottom of the pocket.
• Concentrations in the GCF remained above 16 µg/mL for at least 12 days.
• Mechanical hygiene should be
avoided for 7 days.
Ligosan slow release

47. SUBGINGIVAL MINOCYCLINE
• A locally delivered, sustained-release form of minocycline microspheres
(Arestin)
• Contain minocycline hydrochloride incorporated into a bioresorbable poly
(glycolide-co-D,L-lactide) polymer in unit-dose cartridges.

48. • Each cartridge delivers minocycline hydrochloride equivalent to 1 mg of minocycline
free base .
• Indicated for the reduction of pocket depth in patients with adult periodontitis and as
part of a periodontal maintenance program.
• Its bacteriostatic, antimicrobial activity results from the inhibition of protein
biosynthesis.
• Patients should avoid hard or sticky foods at the treated teeth for 1 week and
interproximal cleaning devices for about 10 days.

49. • The cartridges are stored at 20° to 25° C (68% to 77° F), with excursions
permitted to 15° to 30° C (59° to 86° F).
• Used by injecting the contents of a unit-dose cartridge into the pocket.
• Neither a periodontal dressing nor an adhesive is needed. It is biodegradable
and does not require removal.

50. PLACEMENT OF MINOCYCLINES
MINOCYCLINES

51. SUBGINGIVAL METRONIDAZOLE
• A topical medication that contains an oil-based metronidazole 25% dental
gel (glyceryl mono oleate and sesame oil) .
• As a precursor, the preparation contains metronidazole-benzoate, which is
converted into the active substance by esterases in GCF.

52. • It is applied in a viscous consistency to the pocket, where it is liquidized by the
body heat and then hardens again, forming crystals when it comes in contact
with water.
• Two 25% gel applications at a 1-week interval have been used.

53. Subgingival metronidazole placement

54. SUBGINGIVAL MOXIFLOXACIN
• This antibiotic inhibits cell replication by modifying the actions of DNA gyrase
and topoisomerase IV.
• Since moxifloxacin have antimicrobial activity against aerobic and anaerobic
bacteria, it has been introduced as a local delivery agent for the treatment of
destructive periodontal diseases.

55. Administration of moxifloxacin

56. CLINICALINDICATIONS FOR TREATMENT OF PERIODONTITISWITHADJUNCTIVELOCALDELIVERY
DEVICES
These include
 Local conditions
 Special patient groups

57. LOCAL CONDITIONS
• Deeper pockets (6-8mm range) or furcation involvement
• Management of local non responding sites or disease recurrence during
supportive periodontal care
• When residual pockets are present in the esthetic zone where a surgical
intervention may compromise esthetics or phonetics.
• Sites with deep pockets and persistent bleeding on probing that are associated
with intra bony defects
• Pocket disinfection before regenerative periodontal surgery

58. SPECIAL PATIENT GROUPS
• Smokers
• Diabetic patient
• Cardiovascular patients
• Older patients
• Subjects with relative or absolute contraindications to surgical
intervention

59. FUTURE TRENDS IN LOCAL DRUG DELIVERY
The requirements for treating periodontal disease include a means for
targeting 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 .
Various newer agents are being investigated in the field of local drug
delivery to ensure maximum benefits .

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

61. CONCLUSION
When systemic antibiotics(eg:metronidazole , tetracycline) are used as adjuncts to scaling and
root planing ,provide improvements in attachment levels (0.35 mm for metronidazole; 0.40
mm for tetracycline)
Improvements in clinical attachment levels also occur with the chlorhexidine chip (0.16 mm)
and doxycycline gel (0.34 mm).

62. When scaling and root planing are combined with the subgingival placement of sustained-
release vehicles, further reduction of pocket depths, additional gains in clinical attachment
levels (e.g., 0.39 mm with minocycline gel), and further decreases in inflammation.
The decision regarding when to use local or systemic antimicrobials should be made on the
basis of the clinician's consideration of the clinical findings, the patient's medical and dental
history, the patient's preferences and the benefits of adjunctive therapy with these agents

63. REFERENCE
CARRANZA - CLINICAL PERIODONTOLOGY - 10TH EDITION
CARRANZA - CLINICAL PERIODONTOLOGY - 11TH EDITION
CLINICAL PERIODONTOLOGY AND IMPLANT DENTISTRY - JAN LINDHE – 6TH
EDITION

64. THANK YOU