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Preparation Of Drug Loaded Slow Release Chitosan Membranes And The Pharmacodynamics Investigation Of Paradontosis Therapy

Posted on:2007-03-31Degree:MasterType:Thesis
Country:ChinaCandidate:D XueFull Text:PDF
GTID:2144360182996744Subject:Oral Medicine
Abstract/Summary:PDF Full Text Request
Periodontitis is mainly responsible for adult teeth loss;and itsincidence rate is going up. Periodontitis therapy has long beenfocused on its clinical research. Conventional therapies, includingoral hygiene instruction, scaling, root planning and pocket irrigation,aim to eliminate the local stimulating factors, but fail to arrest orstabilize attachment sites during initial therapy or maintenace. Localantimicrobial therapy has been shown to be an effective treatmentfor periodontitis as an adjunct to mechanical debridement, but hassome side-effects, for example, inaccess to biofilm bacteria andmicrobial resistence. Difficulties in access, extent of periodontaldestruction, unfavourable anatomy and tissue architecture, anddifficulty of plaque control may all limit the effectiveness ofmechanical and antimicrobial therapy. Furthermore, all the abovetherapies could not block the inflammatory cascade reaction in atimely way. Suppression of the bacterial challenge remains the sinequa non of treatment. The ultimate goal of periodotitis therapy is theachievement of periodontal ligament cells (PDLC) are the precursorsfor the regeneration of periodontal tissue,while the undifferentiatedmesenchymal cells in the periodontal ligaments can differentiate intoosteoblasts and cememtoblasts. PDL cells grow and migrate slowerthan gingival epithelial cells,in which case gingival epithelial cellsare the first to cover the root surfaces and form a long gunclionalepithelium. Nevertheless, recognition that the host response topathogens is mainly responsible for tissue destruction has led to hostmodulation therapies in the management of the periodontal patients.In recent years, many researches have been made to explore the hostresponse modulators.Chitosan is the deacetylated (to varying degrees) form of chitin.They both carry positive charge. Chitosan is a linear polymer ofN-acetyl-D-glucosamine and deacetylated glucosamine that sharessome characteristics of glycosaminoglycan and hyaluronic acid. Itexhibits not only excellent biocompatibility and biodegradability, butalso various promising biological activities, such as hemostaticactivity, antimicrobial activity, the ability to accelerate thereformation of connective tissue, angiogenesis and bone formation,the ability to promote the production of transforming growthfactorβ1(TGF-β1)and platelet derived growth factor (PDGF) byhuman monocyte Mφ, the ability to inhibit the overproduction ofprostaglandin E2(PGE2), and many other immune stimulatingactivities. Chitosan, the deacetylated derivative of chitin, is the onlybasic polysaccharide in nature. Special chemical structure brings itinteresting bioactivities, such as antimicrobial, antitumor, immuneenhancing effect and tissue regenerative activities.It has been widelyused in medical field due to its additional biocompatibility andbiodegradability. Because it can be easily formed into film, gel andmicroparticle, so it can meet the necessities of various drug deliverymethods. In addition, its special bioadhesive property helps toprevent the rapid elimination caused by the flushing action of saliva.So chitosan has great application potential in dentalcaries.Peridontitis as an important derivative of chitosan,carboxymethyl chitosan (CMCS) has good water solubility besidesthe characteristic bioactivities and biocompatibility of chitosan.Because of its potential stimulatory effect on the proliferation ofperiodontal ligament cells (PDLCs), it can be formulated intoexcellent guided tissue regeneration (GTR) membrane if itsdegradability and strength can be appropriately controlled byblending with other macromolecular substances or additives. SoChitosan is widely used in the field of biomedicine, especially asdegradable biomaterials in the research field of tissue engineering. Inthis thesis, the research on chitosan membranes has been carried outsystematically, which involved the preparation and characterizationof dense membrane, porous membrane and drug loaded membrane 。Chlorhexidine was loaded into chitosan membranes. This may bebenificial for improving the clinical effect of the membranes.In-vitro release results indicated that drug release rate was very fastat the beginning, and then slowed down, at the final period drugrelease rate speeded up again in some extent. The thickness of themembrane, initial drug content, pH of the in-vitro release media andcrosslinking extent were key factors affecting the in-vitro drugrelease .According to its properties, it is assumed that chitosan producea marked effect on periodontitis. The aim of this study is toinvestigate the therapeutical effect of chitosan medicine loaded slowrelease membrane on periodontitis by clinical evaluation andhistological observations on hybrid dog model of periodontitis andto analyze the involved mechanisms, thereby to provide foundationfor further investigation into chitosan as a new agent of pocket localdelivery.1.The preparation of medicine loaded slow release chitosanmembraneMethod: Prepare some chitosan powder and make it dissolvedinto acetic acid.Add some chlorhexidine acetate powder in it untillits final concentration is 0.1 -0.2 % .Heat untill it dissolves.Finally,shift it into flat plate and decompress and dry it for 72 hourswith vacuum dehydration.Then put it into sodium hydroxide for anhour.Finally clean and dry it .Result :the solution which can makechitosan membrane is colorless and clearing. It's a biscous liquid ofmeta acids .The membrane is yellow and clearing.The surface hasmicrobore.It texture is tenacious and it has a big tensile strength andelasticity.The thickness is about 150 micrometers.We can seeformatio reticularis and 70-120 micrometers aperture size throughSEM.2.Restraining experiment of chitosan to P.g.Method: Misce bene chitosan ,chlorhexidine and compositeresin .We can get chitosan lump with the concentration of 0%,0.5%,1%,2% that's diameter is 6 milimeters . Pre-emergency byultraviolet light disinfection.Place drug loaded lump with different concentration into themedium which inoculated P.g for 72 hours in anaerobic culture .Result:the size of the bacteriostasis circellus enlarged with theincreased concentration.We can see that the bacteriostasis effect ofchlorhexidine loaded chitosan lump is better than simple chitosanlump.It shows that chlorhexidine is bacteriostatic in coordinationwith chitosan.3.The preparation of experiment animal's defect model ofdental capsule and the application of drug loaded chitosan .Methods:experiment animal :4 hybrid dogs.Experiment location:16cheek teeth,( P3,M1) Control group is set up .Gingival flaps wereseparated and bone surfaces were exposed.Then bone outline wasmodified.The right sides were experiment sides. In thecorresponding premolar areas, drug loaded membrane were placedand no membranes in the control areas . The animals were sacrificedat 6 weeks.Decalcified ,embedded, sectioned and HE stained.Result:Eye observations:The gingival attachment healed well, Noinflammatory signs and periodontal bag formations were observed.Screenage show that the frontal resorption of experiment groupconcluded or repaired. However,the frontal resorption range ofcontrol group expanded.Histological anatomy show that theinflammatory infiltration degree of experiment group is much lowerthat the control group.it can be seen regeneration images , neonatalalveolar bone and neonatal cement as well. Conclusion:the aboveresult hint that chitosan medical delayed releasing membrane possessfavourable biology performace.It can not only eliminate bacteriaplaque partly stimulating factor but also block the destroy of alveolarbone with paradentitis to conserve dental capsule.It is a promisinglocal delivery agent for periodontitis and has great therapeuticeffect in GTR.
Keywords/Search Tags:chitosan, slow-release membrane, paradentosis, P.g, GTR, animal model
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