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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE
ANNEXURE – II
PROFORMA FOR THE REGISTRATION
OF SUBJECT FOR DISSERTATION
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NAME OF THE
CANDIDATE AND
ADDRESS
DR.SURYA SURESH PILLAI
FIRST YEAR POSTGRADUATE STUDENT
B.I.D.S
5/3 HOSUR MAIN ROAD
BANGALORE-29
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NAME OF
INSTITUTION
BANGALORE INSTITUTE OF DENTAL
SCIENCES AND HOSPITAL & POST
GRADUATE RESEARCH CENTRE
BANGALORE-560029
3.
COURSE OF STUDY
AND SUBJECT
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DATE OF ADMISSION
MASTER OF DENTAL SURGERY.(MDS)
PERIODONTICS
3 MAY 2010
TO COURSE
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TITLE OF THE TOPIC
“Efficacy of Punica granatum(pomegranate)
incorporated in PLGA, Poly(D-L,lactide-coglycolide)as local drug delivery system in human
chronic Periodontitis-A Clinico-Microbiological
study”
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6.
BRIEF RESUME OF THE INTENDED WORK
6.1 Need for the Study:
Chronic periodontitis is defined as inflammation and destruction of
tooth supporting structure. Periodontal therapy is aimed at arresting the disease
activity and promoting healing of tooth supporting tissues. Although mechanical
periodontal therapy such as scaling and root planning in conjunction with
patient’s plaque control , can arrest this disease activity but occasionally fails and
need surgical treatment to solve the problem. To solve this problem, the
adjunctive treatments such as antimicrobial agents in the form of local drug
delivery systems have been used to overcome the limited efficacy of conventional
periodontal therapy.
Novel drug delivery system is a novel approach to drug delivery that
addresses the limitations of traditional drug delivery systems. However the drug
delivery system used for administering the herbal medicine to patient traditionally
results in reduced efficacy of the drug. If the novel drug delivery technology is
applied in herbal medicine, it may help in increasing the efficacy of the drug.
With this basic idea an attempt is made to evaluate the efficacy of Punica
granatum, a herbal medicine incorporated in biodegradable polymeric
nanoparticle ie PLGA, Poly (D-L,lactide-co-glycolide) as local drug delivery,
adjunct to scaling and root planning in the treatment to Chronic Periodontitis.
6.2 REVIEW OF LITERATURE:
A clinical study conducted by Sastracaha et al (2003) concluded that extracts
of Punica granatum plus scaling and root planning significantly reduced the
clinical signs of chronic periodontitis. An innovative herbal medicament was
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formulated in the form of biodegradable chips for subgingival application .About
20 patients with initial pocket depth 5-8mm were enrolled in the study. After
baseline examination, scaling and root planning of the non-target teeth , the target
teeth received scaling and root planing followed by subgingival delivery of
medicated chips in the test group. The results showed significant improvement
of pocket depth and attachment level in the test sites when compared with
placebo sites at 3 months and placebo and control sites at 6 months.
E. Piñón-Segundo et al (2005) conducted the study to produce and
characterize triclosan-loaded nanoparticles (NPs) by the emulsification–diffusion
process, in an attempt to obtain a novel delivery system adequate for the
treatment of periodontal disease. The NPs were prepared using poly(D,L-lactideco-glycolide) (PLGA), poly(D,L-lactide) (PLA) and cellulose acetate phthalate
(CAP). Poly (vinyl alcohol) (PVAL) was used as stabilizer. Batches were
prepared with different amounts of triclosan (TCS) in order to evaluate the
influence of drug on NP properties. Solid NPs of less than 500 nm in diameter
were obtained. Entrapment efficiencies were higher than 63.8%. The
characterization by scanning electron microscopy and light scattering indicated
that high concentrations of TCS seemingly caused the increase of NP mean size.
A decrease in the PLGA glass transition temperature was observed by differential
scanning calorimetry. This could indicate that TCS in PLGA-NPs behaves as a
non-conventional plasticizer. Subsequently, in vitro release studies were carried
out under sink conditions using a device designed in our laboratory to allow a
direct contact between the particles and the dissolution medium. A fast release of
TCS from NPs was detected. A preliminary in vivo study in dogs with induced
periodontal defects suggested that TCS-loaded NPs penetrate through the
junctional epithelium.
I.Bala et al (2006) conducted a study on sustained release
nanoparticulate formulation containing antioxidant-ellagic (EA) acid as potential
prophylaxis system for oral administration. PLGA nanoparticles were prepared
by a method based on the concept of emulsion–diffusion–evaporation by using
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polyethylene glycol (PEG) 400 as a cosolvent for solubilizing the drug. While
developing this method, didodecyldimethylammomium bromide (DMAB) and
polyvinyl alcohol (PVA), alone and in combination with chitosan (CS) were
employed. DMAB stabilized particles were the smallest of all the formulations
with a particle size of 148.5 nm. PVA alone gave particles of 269.7 nm but a
blend with CS (80:20) resulted in an increase in particle size (359.6 ± 23.6 nm).
Initial release of EA from nanoparticles in pH 7.4 phosphate buffer was rapid,
followed by a slower sustained release. Release rates followed the order
PVA > PVA–CS > DMAB. Release rate from the PLGA–DMAB particles was
slowest, which is attributed to higher hydrophobicity of DMAB as compared to
PVA, preventing diffusion of drug out of polymeric matrix. Insolubility of CS at
alkaline pH could have retarded the release in case of PVA–CS system. In
situ intestinal permeability study of pure drug and the drug encapsulated in
nanoparticles prepared using PVA, PVA–CS blend and DMAB as stabilizer in
rats showed 66, 75, 73 and 87% permeation.
Vasconcelos et al (2006) investigated the antimicrobial effect of
Punica granatum Linn (pomegranate) phytotherapeutic gel and miconazole
(Daktarin® oral gel) against three standard streptococci strains (mutansATCC
25175, sanguis ATCC
10577
and mitis ATCC
9811), S. mutans
clinically
isolated and Candida albicans either alone or in association. The effect of
minimum inhibitory concentrations of the gels on the adherence of these
microorganisms to glass was assessed in the presence of 5% sucrose, using
increasing and doubled concentrations of the diluted solution of the gels ranging
from 1:1 to 1:1024. The minimum inhibitory concentrations of adherence
of Punica granatum L. gel against the test organisms were: 1:16 for S. mutans
(ATCC), S. mutans (CI) and S. sanguis; 1:128 for S. mitis and 1:64 for C.
albicans. The minimum inhibitory concentrations of adherence of miconazole
against the same organisms were: 1:512, 1:64, 1:4, 1:128 and 1:16, respectively.
In experiments with three and four associated microorganisms, the Punica
granatum L. gel had greater efficiency in inhibiting microbial adherence than the
miconazole. The results of this study suggest that this phototherapeutic agent
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might be used in the control adherence of different microorganisms in the oral
cavity.
Alexandre Daher Yunes Salgado et al(2006) conducted a clinical study
on the antiplaque and antigingivitis effects of a gel containing 10% Punica
granatum Linn extract .Twenty three volunteers participated in this cross-over,
double- blind study, carried out in 2 phases of 21 days each. For each period of
the experiment, an acrylic tooth shield was made for each volunteer to carry the
test or placebo gel as well as to avoid brushing of the 4 experimental teeth. The
subjects were randomly assigned to use either the placebo gel (control group) or
the test gel(experimental group) and were instructed to brush the remaining teeth
normally 3 times a day. On days 0 and 21, plaque index and gingival bleeding
index were recorded. The results did not show significant difference between
control group and test group. The gel containing 10% Punica granatum Linn
extract was not efficient in preventing supragingival dental plaque formation and
gingivitis.
M.S.Muthu et al (2010) stated that the biodegradable polyester called
poly(D,L-lactide-co-glycolide )PLGA is the most frequently used biomaterial and
is already commercialized for a variety of drug delivery systems(blends, films,
matrices,microspheres,nanoparticles,pellets,etc).Drug-loadedPLGA nanoparticles
are investigated for targeted and conventional drug delivery systems
for drug
targeting because of their particle size(ranging from 10-1000nm) and long
circulation in blood. Depending on their composition and intended use, these
polymeric nanoparticles can be administered orally, parenterally or locally.
OBJECTIVES OF THE STUDY.
The objectives of this study are:
(1) To assess the minimum inhibitory concentration (MIC) of Punica
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granatum for periodontopathogens in vitro.
(2) To assess the efficacy of Punica granatum as an adjunct to scaling and
root planing.
(3) To compare the efficacy of Punica granatum incorporated in
biodegradable polymeric nanoparticles (PLGA) as an adjunct to scaling
and root planing, with scaling and root planing alone in the treatment of
chronic periodontitis.
7.
MATERIALS & METHODS
7.1 Source of Data:
Patients visiting the outpatient department (O.P.D) of Periodontics, Bangalore
institute of dental sciences and hospital.
7.2 Method of Collection of Data:
Thirty patients of chronic periodontitis with pocket depth 5-8mm around
permanent molars bilaterally will be selected for the study. Sixty selected sites
will be randomly divided into two groups following the split mouth study design.
The test sites will be treated by scaling and root planing and will be followed by
application of Punica granatum incorporated in biodegradable polymer PLGA as
local drug delivery. Control sites will be treated by scaling and root planing
alone.
Following clinical parameters will be recorded for each patient at baseline,
1month, 3 month and 6 month following therapy.
(1)Plaque Index by Sillness& Loe (1964)
(2)Bleeding Index by Muhlemann H.R.& Sons(1971)
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(3)Probing Pocket Depth
(4)Clinical Attachment Level
Subgingival plaque samples will be obtained by using sterile Gracey curettes and
microbial parameters will be assessed at baseline, 1 month, 3month and 6 month.
Statistical analysis will be performed to compare the changes of clinical
parameter and microbiologic parameter between control and test sites at each
interval.
The purpose of this study will be explained to the patient and each patient will
sign the consent form agreeing to comply with maintenance and re-examination
schedule.
INCLUSION CRITERIA:
(1)Patients with chronic periodontitis.
(2)Both male & female patients of 20 yrs of age & above.
(3)Patients with pocket depth 5-8mm and clinical attachment loss≥5mm.
(4) Systemically healthy subjects.
EXCLUSION CRITERIA:
(1)Patients allergic to the medication used in this study.
(2)Patients who have received antibiotic therapy 3 months prior to the study
enrolled.
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(3)Patients with history of periodontal treatment 6 months prior to the study
enrolled.
(4)Systemically compromised patients.
(5)Pregnant or lactating women.
(6)Physically and mentally challenged subjects.
7.2 Does the study require any investigation or intervention
to be conducted on the patients or other animals?
Yes. Microbiological investigation will be done.
7.3 Has ethical clearance been obtained from your
institution?
Yes.
Ethical approval has been sought and obtained for the study from the
institution.
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8.
LIST OF REFERENCES
(1) Sastracaha, G., P. Yotnuengnit, P. Booncong, and P. Sangtherapitikul.
(2003) Adjunctive periodontal treatment with Centella asiatica and Punica
granatum extracts. A preliminary study. Journal of the International Academy of
Periodontology ; 5(4): 106-115.
(2) Piρσn-Segundo E, Ganem-Quintanar A, Alonso-Pιrez V, QuintanarGuerrero D (2005) Preparation and characterization of triclosan nanoparticles
for periodontal treatment. Int J Pharm 2005; 294:217-32.
(3)I. Bala, V. Bhardwaj, S. Hariharan, S.V. Kharade, N. Roy and M.N.V.
Ravi (2006) Sustained release nanoparticulate formulation containing
antioxidant- ellagic acid as potential prophylaxis system for oral administration.
journal of drug targeting; 14(1): 27-34.
(4) Vasconselos, L.C, F.C. Sampaio, M.C.Sampaio, S.Pereira Mdo, J.S.
Higino and M.H.Peixoto(2006). Minimum Inhibitory concentration of
adherence of Punica granatum Linn (Pomegranate) gel against S.mutans, S.mitis
and C.albicans. Brazilian Dental Journal; 17(3):223-227.
(5)Alexandre Daher Yunes SALGADO,Juliana Lemos MAIA ,Sergio LUIS
da Silva PEREIRA, Telma leda Gomes de LEMOS, Olivia Morais de Lima
MOTA(2006).Antiplaque and Antigingivitis effects of a gel containing Punica
granatum Linn extract.A Double-Blind Clinical Study In Humans.J Appl Oral
Sci;14(3):162-165
(6) M.S.Muthu (2010).Nanoparticles based on PLGA and its co-polymer: An
overview. Asian journal of Pharmaceutics; 99(2):266-270.
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9.
Signature of Candidate
10.
Remarks of the Guide
Surya Suresh
DR.APARNA RAHUL
PROFESSOR AND HEAD,
11.1 Guide
DEPARTMENT OF PERIODONTICS,
B.I.D.S
BANGALORE,560029
11.2 Signature
11.3 Co-Guide
11.
11.4 Signature
DR.APARNA RAHUL
PROFESSOR AND HEAD,
11.5 Head of the
Department
DEPARTMENT OF PERIODONTICS,
B.I.D.S
BANGALORE,560029
11.6 Signature
12.1 Remarks of the
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Chairman and Principal
12.2 Signature
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