Study Of Periodontal Sustained Release Preparation Of Doxycycli-Ne Hydrochloirde

Periodontitis is a chronic destructive disease of inflammatory invasion ofgingival and periodontal support tissue,It’s a major cause of tooth loss inadults. Doxycycline hydrochloride （doxycycline hydrochloride, DXY） couldeffectively inhibit the periodontal pathogens,promote periodontal regeneration,and inhibiting bone resorption.In order to reduce the side effects of systemicadministration, enhance the therapeutic effect,reduce the frequency of admi-nistration,improve the medication compliance of patients,This subject develo-ped periodontal sustained-release preparation of doxycycline hydrochloridewas developed in this subject.In this topic, carboxymethyl chitosan （Carboxymethyl chitosan，CMCTS）was chosen as a carrier material. The carboxymethyl chitosan microspheresloaded DXY（DXY-CMCTS-MS） were carried out by emulsifyingcross-linking process. The facors that effected the microsheres characteristicswas investigated such as the stirring rate, curing time, the amount ofcrosslinker, the ratio of oil and water, CMCTS concentrations, theoreticalloading, the amount of emulsifier.Three factors that had an important effectson microsphere preparation was selected to optimize furtherly.The threefactors was as following: the dosage ratio: the mass ratio of DXY to CMCTS;the volume percentage of the oil and water phases; the amount of crosslinkerformaldehyde.With drug loading,encapsulation efficiency and yield asindicators,the three factors and five levels of the Star point response surface method was used to optimize the formulation and preparation process.Scanning electron microscopy and optical microscopy was used to observethe surface morphology of the microspheres.After the formulation andpreparation process optimization,DXY-CMCTS-MS with a global shape,sharp edges and narrow distribution were prepared.The average diameter was（25±8.0）μm, the drug loading rate was18.9%and the encapsulation efficiencywas64.6%.Chitosan temperature hydogel composite with the microspheres wasprepared.DXY-CMCTS-MS was blended with the solution of chitosan-β-glyc-erophosphate,and keep magnetic stirring until the microspheres wereuniformLy dispersed.The factors effected the gel formed was studied withgelation time as an index.The microsphere gel composite carrier waesemisolide that could freely flow at the room temperature and it could rapidsolidify under37℃,The gelation times was1.1±0.3min.The dynamic membrane dialysis method and UV spectrophotometricmethod were used to determine in vitro release characteristics of the DXYmicrospheres and DXY microspheres temperature-sensitive gel.The resultsshowed that the rate of drug release was slower with the impovement of thepH of release medium,the amount of crosslinking agent and curing time. Drugrelease rate was lessen with the decrease of the drug/carrier ratio. With theincreasing of the chitosan concentration, drug released form carrier wasreduced. when composite the microspheres and gel,the release rate wassignificantly decreased when the microspheres was composited with the gel.The release curve meeted Higuchi fitting equation: y=20.983x-1.3113（R²=0.9911）.This study used the Wistar rats as experimental subjects. Endotoxin wasinjected every other day to establish the animal model of periodontitis.The ratswere randomLy divided into three groups, the blank control group （D） was not handling, dosing group （G₁） was given homemade DXY microspherestemperature-sensitive gel, positive control group （G2） was given commerciallyavailable drugs Periocline ointment. After treatment of3w, the Sulus bleedingindex, Periodontal index, probing depth, plaque index, amount of bone losswere measured and the histopathological sections was observed.The resultsshowed that administration groups （G₁） and positive control group （G2）compared with the balnk control group had significant differences （P <0.05）,while the administration group （G₁） and the positve control group （G2）showed no significant difference （P>0.05）. Histopathological observationsfound that the inflammation of administration groups （G₁） and the positvecontrol group （G2） were significantly improved, there was a small amont ofLymphocyte infiltration, periodontal ligament cells arranged in the same,relatively smooth surface of the alveolar bone, rare osteoclasts and resorptionpits.It was showed in this paper that DXYmicrospheres composited withtemperature-sensitive gel was significantly effective on periodontitis.