the presentation explains the basics behind use of local drug delivery in periodontics

1. LOCAL DRUG
DELIVERY
Presented by Dr. Aishvarya Hajare
Second yr postgraduate
Department of Periodontics
1

2. CONTENTS
• Introduction
• Historical perspective
• Terminology
• Classification of local
antimicrobial therapy in
periodontics
• Indications
• Contraindications
• Advantages
• Disadvantages
• Systemic Versus Local Drug
Delivery
• Requirements For Local
Antimicrobial Agents
• Drug delivery devices for
intrabony pocket
• Locally delivered antimicrobials
• Recent advances in LDD
• Conclusion
• References
2

3. INTRODUCTION
• Periodontitis is defined as a multifactory disease involving inflammatory changes
of the supporting tissues of teeth caused by specific organisms or a group of
specific organism, resulting in immune response leading to progressive
destruction of periodontal ligament and alveolar bone.
• Non surgical & surgical therapy is both applicable in treatment of periodontal
disease. However the mechanical debridement itself may not always reduce or
eliminate the pathogens.( Van winkelhoff AJ et al. 1996)
3

4. • Shortcomings associated with mechanical debridement lead to addition of both
systemic and locally antimicrobial therapy to enhance treatment & serve as an
adjuncts to mechanical therapy.
• Systemic antimicrobials agents may reduce or eliminate bacteria that cannot
be removed by scaling and root planning.
• However adverse effects such as drug toxicity, acquired bacterial resistance,
drug interaction and patient’s compliance limit the use of systemic
antimicrobials.( Golombg et al. 1984)
4

5. HISTORICAL PREVIEW
• 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, the efficacy to side effects.
• 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’.
• Dr. Max GoodSon (1979) who championed and developed controlled release local
delivery of therapeutic agents into a viable concept.
5

6. TERMINOLOGIES
• 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.
• Controlled release local delivery: Implies release of chemotherapeutic agents into
the periodontal pockets over an extended period of time, provides prolonged drug
availability, and sustained drug action.
7

8. 1. LANGER AND PEPPAS (1988) Classified controlled drug release polymeric
system based on their mechanism of action.
• I. Diffusion controlled systems
• A. Reservoirs (membrane
devices)
• B. Matrices (monolithic device)
• II. Chemically controlled systems
• A. Bio-erodible systems
• B. Pendant chain systems
• III. Solvent activated systems
• A. Osmotic system
• B. Swelling controlled system
• IV. Magnetically controlled systems
8
CLASSIFICATION OF LOCAL ANTIMICROBIAL
THERAPY IN PERIODONTICS

9. 9

10. Kornman (1993) classified the Controlled Release Local Delivery System
• A. Reservoirs without a rate controlling system like hollow fibers, gels and
dialysis tubing.
• B. Reservoirs with rate controlling system like erodible polymeric
matrices, microporous polmer membrane, monolithic matrices and coated
drug particles.
10

11. Rams and Slots (1996) based on type of therapy
1. Personally applied (patient home self care)
A. Non- sustained subgingival drug delivery ( home oral irrigation)
B. Sustained subgingival drug delivery
2. Professionally applied (in dental office)
A. Non-sustained subgingival drug delivery (professional pocket irrigation)
B. Sustained subgingival drug delivery ( controlled release device)
11

12. Soskolne WA (1997) developed in three broad dosage forms :
• A. Fibers - tetracycline
• B. Films/ slabs- eg. Chlorhexidine chip
• a) non degradable films
• b) degradable devices
• C. Injectable devices eg. Minocycline
12

13. Greenstein and Tonetti (2000) according to the duration of drug
release
• 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.
films administer once
follow zero order kinetics
13

14. INDICATIONS:
• Periodontal patients with successful phase I therapy
• Periodontal patients who are medically compromised where surgical therapy is
contraindicative.
• In combination with mechanical debridement or alone.
• In-patients who are suffering from recurrent or refractory periodontitis.
• During periodontal regenerative procedures.
14

15. CONTRAINDICATIONS:
• Periodontal patients with known hypersensitivity reaction to any of the antimicrobials
used for periodontal therapy.
• With local delivery of Metronidazole preparations, contraindicated in alcoholics.
• Patients susceptible to infective endocarditis are contraindicated for irrigation devices
to avoid the risk of bacteremia.
• Delivery of antimicrobial agents using ultrasonic scalers is contraindicated in
asthmatics, infective conditions (AIDS, TB) and those with cardiac pacemakers.
15

16. ADVANTAGES:
• Local drug delivery can attain 100 folds higher concentrations of the agent in
subgingival sites compared with a systemic drug regimen.
• Local delivery may employ antimicrobial agents not suitable for systemic
administration.
• Personally applied antimicrobial regimens offer the potential of daily placement into
pockets, for compliant patients.
• Professionally applied antimicrobial regimens reduce potential problems with
patient compliance that place the use of systemic drug regimens.
• Local antimicrobial delivery reduces the dangers associated with systemic
administration such as toxicity, adverse reactions, resistant strains and
superimposed infections.
16

17. DISADVANTAGES:
• Difficulty in placing antimicrobial agents into deeper parts of pockets and
furcation lesions.
• Patient compliance and manual dexterity are limiting factors in the case of
personally applied antimicrobial regimens.
• Professionally applied antimicrobial therapy is time consuming and labour
intensive in-patients with numerous advanced lesions.
• Locally applied antimicrobial agents do not markedly affect pathogens residing on
extra-pocket oral surfaces.
• Non-sustained drug delivery provides only a brief exposure of the target
microorganism to the applied antimicrobial agent. 17

18. SYSTEMIC VERSUS LOCAL DRUG
DELIVERY:
•1. Route of
administration
•2. Pain/Discomfort
•3. Drug dosage
•4. Peak levels
•5. Pharmacokinetics
•6. Frequency
•7. Super infection
•8. Microbial resistance
Systemic
•Orally or Parental
•Not painful
•Higher drug dosage(in
mg)
•Few hours in plasma
•Distribution in various
compartments where
antimicrobial effect may
not be reqd.
•Once in 6-12 hours
•Present
•Present
Local drug delivery
•Site Specific
•Nil
•Lower dosage (in
micrograms)
•Within few minutes in
GCF
•Minimal body
distribution to different
compartments with max
concentration at delivered
sites.
•Usually once a week
•Limited
•Limited
18

19. •9.Patients
compliance
•10.Time required
•11. Side effects
•12. Effects of
conn. 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
required
•Limited
•Limited
19

20. REQUIREMENTS FOR LOCAL ANTIMICROBIAL
AGENTS
• Safety
• Stability
• Substantivity
• Efficacy
• Adequate subgingival delivery
• Achievement of effective concentrations
• Biodegradable
• Retention after placement
• No emergence of bacterial resistance
• Should be effective only against periodontal pathogens and not on commensal
microflora.
• Cost-effectiveness and patient compliance. 20

21. DRUG DELIVERY DEVICES FOR
INTRAPOCKET THERAPY
• Fibers- are thread – like devices placed in periodontal pocket and secured with
periodontal dressing, ensuring a sustained release of drug at the site.
• Several polymers such as
• poly(ecaprolactone) (PCL),
• polyurethane,
• polypropylene,
• cellulose acetate propionate and
• ethyl vinyl acetate (EVA)
21

22. • Films- are implantable matrix delivery devices with
encapsulation of drug, in a manner that they are distributed
throughout the polymer and control release occurs by drug
diffusion and/or matrix dissolution or erosion.
• Films that release drugs by diffusion alone are prepared by
using water-insoluble non-degradable polymers, whereas
those that are released by diffusion and matrix erosion or
dissolution use soluble or biodegradable polymers.
• Should not exceed 400micrometer.
22

23. Gels- are injectable semi solid devices containing an
adequate concentration of drug and delivered at
specific site.
They are easy to prepare and administer.
Also a property of bioadhesivity that enhances the
retention time in the periodontal pocket.
23

24. • Microparticulate system- consists of an encapsulation of the drug
into a polymer, which dissolves gradually releasing the drug at
the target site.
• Poly lactide (PLA) or poly (lactide – co-glycolide) PLGA
microspheres containing minocycline have been formulated and
have been used for the elimination of Porphyromonas gingivalis
from the periodontal pocket .
24

25. • Nanoparticulate system- Modern drug delivery systems are designed for targeted controlled slow
drug release.
• It provides several advantages as compared with microspheres, microparticles and emulsion-
based delivery systems, including high dispersibility in an aqueous medium, controlled release
rate and increased stability.
• Due to their small size, nanoparticles penetrate regions that may be inaccessible to other
delivery systems, such as the deep periodontal pockets.
25

26. • Three preliminary studies have been conducted to assess the efficacy of nanoparticles in
periodontal drug delivery.
• Dung et al in 2007 used Antisense oligonucleotide- loaded chitosan tripolyphosphate (TPP)
nanoparticles and showed the sustained release of oligonucleotides which is suitable for the
local therapeutic application in periodontal diseases.
• Pinon et al in 2005 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.
• Moulari et. al in 2006 investigated the in vitro bactericidal activity of the Harungana
madagascariensis leaf extract (HLE) using the poly (D,L-lactide-co-glycolide) nanoparticles
(PLG-NP) on the oral bacterial strains largely implicated in dental caries and gingivitis
infections and diminution of the bactericidal concentration compared to HLE
26

27. • Vesicular system
• Vesicular liposomal systems are designed to mimic the bio-membranes in terms of structure and
biobehaviour, and hence are investigated intensively for targeting periodontal biofilms.
• The targeting of liposomes was thought to be because of the interaction of the polyhydroxy groups
of liposomes with surface polymers of the bacterial glycol-calyx.
• Succinylated Concanavalin-A (lectin)-bearing liposomes (proteoliposomes) have been found to be
effective for the delivery of triclosan to periodontal biofilms.
• The potential of lectin-bearing liposome systems as a targeting system for the control of gingivitis
and dental plaque has been extensively studied Vyas SP 2001
27

28. LOCALLY DELIVERED ANTIBIOTICS/ANTIMICROBIALS
IN PERIODONTAL THERAPY
• TETRACYCLINES
• The tetracyclines were introduced into clinical practice in the late 1940s.
• They have ability to concentrate in the periodontal tissues and inhibit the growth of A.
actinomycetemcomitans.
• Properties of tetracycline such as collagenase inhibition, anti-bone resorption effect,
anti-inflammatory actions and fibroblast attachment are of value in management of
periodontal diseases. (Soares PB 2009 and Seymour RA 1995)
29

29. • Tetracycline fibers are commercially available as Actisite® (tetracycline periodontal)
periodontal fiber for periodontal pocket placement consists of a 23 cm (9 inch) monofilament of
ethylene/vinylacetate copolymer, 0.5 mm in diameter, containing 12.7 mg of evenly dispersed
tetracycline hydrochloride, USP Actisite® (tetracycline periodontal) fiber provides continuous
release of tetracycline for 10 days.
30

30. • Goodson et al 1991 showed better results with tetracycline therapy alone than the scaling and root
planing.
• Litch in 1997: Suggested excellent improvement in clinical parameters such as plaque index,
gingival index, pocket depth when used in combination of SRP and actisite, than actisite or SRP
alone.
• Tariq et al in 2012 observed improvement in clinical parameters of gingival inflammation with all
the three treatment modalities: SRP alone, tetracycline fiber therapy alone and combined therapy of
SRP+TCN fibers,
• According to Drisko et al 1995 and Michalowicz et al 1995, Goodson et al 1985, Blamlof et al 1989
Southard et al 1989, and Christersson et al 1993 observed significant reduction in pocket depth after
chemical conditioning of the root surface without subgingival scaling and application of tetracycline
fibers into the pockets.
31

31. • The other commercially available formulation is periodontal plus AB.
• A collagen fibril based formulation contains tetracycline hydrochloride (2 mg of tetracycline) in
which 25 mg are collagen fibrils that can be directly applied for all levels of periodontal
infections.
32

32. Gel
• Tetracycline-Serratiopeptidase-Containing Periodontal Gel Formulation has shown
statistically significant results along with scaling and root planing.
• Bioerodible Injectable Poly (ortho ester) for Tetracycline Controlled Delivery
formulations loaded with tetracycline 10% or 20% showed complete in vitro
degradation concomitant with drug release.
33

33. • DOXYCYCLINE
• Doxycycline (DOX) is a broad-spectrum antibiotic synthetically derived from oxytetracycline.
• It is bacteriostatic, inhibiting bacterial protein synthesis due to disruption of transfer RNA and
messenger RNA at ribosomal sites.(Perno M. 2001)
• It is effective in significantly reducing collagenase activity in the GCF and gingival inflammation
(McCulloch 1990,Aitken 1992, Matisko 1993).
34

34. • Commercically available Atridox (for subgingival delivery of doxycycline) 10% is indicated for
use in treatment of chronic adult periodontitis to gain clinical attachment, and reduce probing
depth and bleeding on probing.
• 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
• Syringe B contains doxycycline hyclate which is equivalent to 42.5 mg doxycycline.
• The constituted product is a pale yellow to yellow viscous liquid with a concentration of 10% of
doxycycline hyclate
35

35. 36

36. • MINOCYCLINE
• Minocycline is a semisynthetic derivative of tetracycline and a very potent broad
spectrumantibiotic. Minocycline works by interfering with protein synthesis in the
bacterial cell wall.
• It has been used clinically to treat gingivitis, acute necrotizing ulcerative
gingivitis, chronic periodontitis, and aggressive periodontitis.
37

37. • 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.
38

38. • Microsphere
• Commercially under the trade name of Arestin™Technology employs microencapsulated
minocycline hydrochloride in a bioabsorbable polymer as the vehicle (polyglycolide-co-dllactide
[PLG]).
• The 2% minocycline is encapsulated into bioresorbable microspheres (20-60μm in diameter) in
a gel carrier and has resorption time of 21 days.
39

39. • Ointment
• Minocycline ointment is a bioabsorbable sustained delivery system consisting of 2%
minocycline hydrochloride in a matrix of hydroxyethyl-cellulose, aminoalkyl-methacrylate,
triacetine and glycerine.
• Dentomycin (2% Minocycline gel) has received regulatory approval for the treatment of
periodontitis in the European Union.
• The same product is available in Japan with the name Periocline.
40

40. • Musalaiah, vandana K.L., Mehta D.S.in suggested that excellent improvement in clinical
parameters such as plaque index, gingival index, pocket depth used in combination of SRP
and dentomycin 2% gel, than dentomycin 2% gel, SRP alone.
• According to Kurimoto et al (1987), Landry et al (1992) Van Steenberghe et al (1993),
Jones (1994), who observed a significant reduction in pocket depth with minocycline
hydrochloride 2% gel as an adjunct to scaling and root planing in the treatment of chronic
adult periodontitis.
41

41. • Chlorhexidine gluconate
• Chlorhexidine gluconate is an antimicrobial agent active against a wide spectrum of gram-
positive and gram-negative organisms, yeast, fungi, facultative anaerobes and aerobes.
• In 1970, Loe and Schiott reported a total inhibition of new plaque formation and prevention of
the development of gingivitis by an aqueous solution of 0.2% chlorhexidine digluconate in the
form of a mouthrinse.
• Its mechanism of action relates to
Reduction in pellicle formation,
Alteration of bacterial adherence to teeth, and
An alteration of bacterial cell wall causing lysis.
42

42. • Its antibacterial action is due to an increase of the cellular membrane permeability,
followed by the coagulation of intracellular cytoplasmic macromolecules.
• Because chlorhexidine is highly cationic, it exhibits high substantivity.
• Its chemical structure allows it to remain in the oral cavity for a prolonged period after a
single rinse and thereby function in a slow release type manner.
43

43. • Film
• Periochip (Dexcel Pharmaceuticals, Israel) is an orange brown, biodegradable, rectangular chip
rounded at one end that has an active ingredient of chlorhexidine gluconate (2.5 mg) that is
released into the pocket over a period of 7-10 days.
• The polymer is made from 3.4 mg of cross-linked hydrolysed gelatin, 0.5 mg of gelatin and 0.96
mg of purified water , a n d contains 2.5 m g chlorhexidine. It measures 5x4 mm in size and 0.35
mm thickness.
44

44. • Srinivas Reddy N., Shobha Prakash, Mehta D.S Suggested a significant reduction in clinical
parameters like plaque index, gingival index, gingival bleeding index, probing pocket depth
when used in combination of SRP and perio-chip 2.5 mg chlorhexidine gluconate, than
perio-chip or SRP alone.
• Jeffcoat et al (1997) who studied the SRP alone and SRP+periochip, in which SRP+periochip
showed significant reduction in probing depth when compared to SRP alone.
• Finally it can be suggested that subgingival delivery of biodegradable 2.5mg chlorhexidine
gluconate chip form can be effective when associated with mechanical debridement in the
treatment of chronic adult periodontitis
45

45. • 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.
46

46. • Metronidazole
• Metronidazole is selectively toxic to anaerobic microorganisms.
• After entering the cell by diffusion, its nitro group is reduced by certain redox proteins
operative only in anaerobic microbes to a highly reactive nitro radical which exerts
cytotoxicity, by damaging DNA and other critical biomolecules.
47

47. • A topical medication Elyzol® containing oil based metronidazole 25% dental gel (glycerol
monooleate and sesame oil) is available for local application.
• On contact with the gingival fluid, it forms a highly viscous gel.
• Estimated dose of Metronidazole per treated tooth was 3mg and drug concentration in GCF
after one day was 1g/ml.
48

48. • Kiran Joseph, Vandana K.L. suggested that within all the treatment groups i.e. SRP,
SRP+Elyzol, Elyzol alone there was a significant reduction in all the clinical parameters
such as plaque index, gingival index, gingival bleeding index and probing pocket depth
from baseline to the 42 day.
• Palmer R.M. et al (1998) divided his treatment groups randomly into (SRP,
SRP+systemic Metronidazole, SRP+gel) and found no statistical significant differences in
probing pocket depth between the groups.
49

49. • Collagen sponges containing 5% metronidazole with trade name METROGENE
(SEPTODENT, FRANCE) which is intended to be inserted into periodontal pocket. It is a
new combination of two known substances; bovine collagen (Type I) 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).
• Tony P. Paul, Vandana K.L., Mehta D.S. suggested that significant improvement in
clinical parameter such as plaque index, gingival index, pocket depth used in
combination of SRP and metrogene, than metrogene, SRP alone.
50

50. Drugs for osseous defects
• ALENDRONATE
• Alendronate a novel bisphosphonate is a very potent inhibitor of bone resorption.
• The net effect of alendronate on bone formation is its inhibition of osteoclasts thus affecting the
bone maturation and remodelling.
• Once taken up by the bone alendronate has a prolonged skeletal retention (half life upto several
years) and significant amount can be released in the resorptive process which may in turn
protection to alveolar bone. (Binderman I et al. 2000 and Veena HR 2010)
51

51. • SIMVASTATIN
• Statins like simvastatin (SMV), lovastatin, and pravastatin are specific competitive inhibitors
of 3-hydroxy-2-methyl-glutaryl coenzyme A (HMGCoA) reductase.
• Statins modulate bone formation by increasing the expression of bone morphogenetic protein-
2, inflammation, and angiogenesis, thus providing a new direction in the field of periodontal
therapy.(Morris MS 2008 and Avani R. Pradeep 2010 )
52

52. • IPRIFLAVONE
• Ipriflavone (7-isopropoxy iso-flavone) is a synthetic isoflavone derivative that acts primarily
to suppress bone resorption.
• Min et al.2008 evaluated effect of ipriflavone on periodontal reorganization and revealed
that it shows more rapid effect.
• Perugini et al.2008 designed a film dosage form for sustained delivery of ipriflavone into the
periodontal pocket. A monolayer composite systems made of ipriflavone loaded poly
micromatrices in a chitosan film form, were obtained by emulsification/evaporation/casting
technique. They demonstrated that the composite micromatricial films represent a suitable
dosage form to prolong ipriflavone release for 20 days
53

53. 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.
54

54. • Aloe vera
• Aloe vera possess certain active components such as saponins, anthraquinones, amino acids,
lignin, salicylic acid, etc., in which anthraquinones have the strong anti-bacterial, anti-viral and
anti-neoplastic properties.
• Virdi et al. in 2012 evaluated the effect of A. vera gel in patients with chronic periodontitis and
found that group in which A. vera gel was applied as an adjunct to scaling and root planning
showed significantly better results than scaling and root alone.
55

55. • Eucalyptus
• Eucalyptus (Nagata H et al. 2008 ) used improved oral health status.
• Ethanol extracts (60% ethanol) from Euclyptus globulus leaves reportedly possess
antibacterial activity against various bacteria, including oral bacteria.
• Moreover, 60% ethanol extracts from the E. globulus leaf displayed antibacterial
activity against several periodontopathic bacteria, including Porphyromonas
gingivalis and Prevotella intermedia. (Hideki Nagata et al. 2008)
56

56. • Neem
• Neem extract contains
• (i) Azadiractin - the active principle,
• (ii) Glycosides -antimicrobial,
• (iii) Sterols
• (iv) Luminols-anti-inflammatory and
• (v) Flavenoids.
• Neem has showed better efficacy in the treatment of oral infections and plaque growth
inhibition in treating periodontal disorders.
• Neem extract gel produced more improvements in clinical as well as microbiological
parameters than the control. The approach of local delivery of a natural extract with no known
side effects has proved promising results. (Dr. Verdine Virginia Antony et al 2013)
57

57. • Turmeric
• It has proven properties like
 Anti-inflammatory
 Antioxidant
 Antimicrobial
 Hepatoprotective
 Immunostimulant
 Antiseptic
 Antimutagenic and
 It also accelerates wound healing.
 A study was done to evaluate the adjunctive efficacy of turmeric, curcumin, and
traditional nonsurgical methods for treating periodontal pockets.
 Plaque index and gingival index scores showed significant improvement from baseline
through the end of the study.(Kudva P et al 2012)
58

58. • Bloodroot
• Due to its natural alkaloids, bloodroot can curb thegrowth of bacteria responsible for
periodontal disease.(ChopraR. N 1956)
• Local application of sanguinarine via a controlled release system showed low clinical
efficacy.
• The reason for this may be due to its conversion to the pseudobase form. This
conversion has been shown to occur above pH 6.0 leading to increased insolubility
and resulting in reduced bioavailability.
• With the pH of gingival crevicular fluid (GCF) in a periodontal pocket being in the
range of 7.5±7.9, it is the likely cause of the sanguinarine conversion to its less
bioavailable form.
59

59. LOCAL DRUG DELIVERY’S IMPACT ON
DEEP PROBING DEPTHS (≥7 MM)
• Garrett et al reported that when doxycycline gel was compared to SRP, it achieved equivalent
results with regard to probing depth reduction at sites initially 7 mm deep.
• Drisko et al reported that at sites ≥ 7mm tetracycline fibres versus SRP attained PD reduction
that were not statistically significant.
• Similar results were obtained with minocyline microspheres ( Williams et al in 1996)
• Timmerman et al reported that there was no benefit of employing 2% minocycline gel as an
adjunct to SRP to reduce probing depths at deep sites.
• Steenberg et al noted that combined therapy provided a better result than SRP alone at sites
≥7mm deep.
60

60. REPAIR OF OSSEOUS DEFECTS
• Meimberg et al in 2001 used subtraction radiography to detect 0.5mm bone height gain
in 4 % pts treated with combined therapy of minocycline + SRP & a similar
imporvement was noted in SRP alone
• Aimette et al in 2004 reported that tetracycline fibres + SRP resulted in 0.94mm bone
deposition in osseous defects versus 0.09mm after SRP alone.
• In general results regarding bone fill need to be interpreted in light of the fact that
other clinical procedures provide better bone repair in osseous defects
61

61. EFFECT OF LDD ON FURCATIONS
• Tonetti et al reported that tetracycline fibers in conjunction with SRP initially provided a
better result than SRP alone at molar furcations; however, after 6months, therewere no
statistically significant differences with respect to mean probing depth reduction or gain of
clinical attachment.
• Williams et al and Meimberg et al noted a statistically significant greater probing depth
reduction in molar furcations when SRP plus minocycline microspheres were compared to
SRP alone
62

62. OVERVIEW OF PERIODONTAL
IMPROVEMENTS ACHIEVED WITH LOCAL
DRUG DELIVERY
• When four devices (tetracycline fibers, doxycycline gel, minocycline microspheres, and
metronidazole gel) were evaluated as monotherapies (used without mechanical instrumentation)
and compared to SRP alone there were no statistically significant differences between therapies
relative to decreasing probing depth and gain of clinical attachment.
• At present, doxycycline gel is the only local delivery device approved by the Food and Drug
Administration (FDA) as a monotherapy for treatment of chronic periodontitis.
• Overall, mean probing depth reduction for these delivery systems when used as a monotherapy at
sites initially 4 to 6 mm deep was around 1 mm. However, larger probing depth decreases were
reported in deeper pockets with tetracycline fibers and doxycycline gel.
• A systemic review supports the adjunctive use of local antimicrobialsto debridement in deep or
recurrent periodontal sites, mostly when using vehicles has proven sustained release of the
antimicrobial.(Matesanz-Pe´rez P 2013)
63

63. • A meta-analysis conducted on use of antimicrobial sustained-release systems as an adjunct to
SRP concluded that it does not result in significant patient-centered adverse events.
• Local drug delivery combined with SRP appears to provide additional benefits in PD reduction
compared with SRP alone. (Rupali Kalsi 2011)
64

64. Recent advances in local drug delivery
• Some of the delivery challenges described above have led to research into technologies such
as mucoadhesives, permeability enhancers and enzyme inhibitors as well as modifications to
drugs and absorption enhancers that could enhance both topical and systemic transmucosal
delivery of drugs.
65Hearnden V et al. 2012Advanced Drug Delivery Reviews. 2012; 64: 16-28.

65. CONCLUSION
• The periodontal drug delivery systems are which are mucoadhesive, biodegradable
nanoparticles technology has an immense opportunity for the designing of a novel, low-dose and
effective treatment method by the use of the intra-pocket controlled device.
• These devices are proving to be more convenient, easy-to-use and more effective than the
regular drugs and medicines which act systemically.
• These devices also do not probe the risk of overdose or systemic overload, simple for
formulation, affordable and easily available.
66

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