Experimental Study On Treating Periodontits With Sustained-release Gel

Periodontitis is one of the familiar dental diseases and it is a main cause which leads to tooth loss .There is no efficient method to cure it at present. it is a complicated inflammation which is caused by gram-negative anaerobic bacteria . It has been known that tinidazole and tetracycline can kill these bacterias , but the effect is not very good owing to the short sustained time and large side effect . The sustained-release formula can solve these problems and it is a pathway of periodontitis' s studying.Sustained-release gel have two key elements : efficient drug and sustained-release meterial. Besides the effect of killing bacteria, doxycycline can also inhibit the activity of matrix metalloproteinase(MMPs) by many ways such as reducing the breakage of conjunctive tissue and stoping the progress of periodontitis. Recombinant human bone morphogenetic protein-2(rhBMP-2) has bone inductive activity and can promote periodontal ligament cell(PDLC)to be differentiated into osteoblast. It can also promote the regeneration of alveolar bone and cementum which can induce the growth of parodontal membrance . Poly lactic and glycollic acid(PLGA) is a kind of biodegradable material . The efficient drug which was mixed in the gel will release slowly alone with the degradation of PLGA , so it can reach the aid of continuous action . Because of the different molecular weight and different proportion between lactic acid (LA) and glycollic acid(GA) , the degradation speed of PLGA is also different .The gel was made using PLGA as sustained material, including doxycycline and rhBMP-2 as treating drugs. The gel' s performance and coagulate time were measured. The best formula and the efficient of sustained-release gel were tested .This study consists of two sectionsSection one preparation of sustained-release gel and in vitro testThe aid of this study is to develop a good sustained-release gel which can be used in practice , it should accord the following characteristics:1. PLGA will become gel when it is dissolved in mixed solvent and it has the characteristic of fluidity and stickiness.2. The gel coagulate within 10-15 seconds after touching water.3. The gel dissolve within 7-10 days, the drug mixed in the gel release slowly alone with the breakdown of gel.4. rhBMP-2 which was mixed in the gel has biologic activity.In order to reach these aids ,this study use PLGA75:25 ( average molecular weight is below 10 thousand)and PLGA80:20(average molecular weight is near 20 thousand) as the sustained-release material.The concentration of PLGA75:25 are 25w/w% , 30w/w% & 35w/w% separately, the concertration of PLGA80:20 are 9w/w% , 12w/w% & 15w/w% separately , the mixed solvent consist of 2 kinds of solvent: IMP and GTA,the proportion of the 2 solvent is 6:4 ,7:3 ,8:2 separately , and the concentration of doxcycline is 6w/w% ,9w/w% & 12w/w% prepare 18 kinds of gel following the method of orthogonal design .Measure the concentration of doxycycline in water and PBS at the different times , filter out the best formula according with its releasing.The result showed: for the PLGA80:20 , the gel don' t coagulate when the concentration of PLGA below 4w/w% .According to the orthogonal score , we get the best formula:concentration of PLGA80:20 is 14w/w% , 1MP:GTA=7:3 , concentration of doxycycline is 6w/w%.For the PLGA 75:25, the gel don' t coagulate when the concentration of PLGA below 10w/w% . According to the orthogonal score , we get the best formula : concentration of PLGA is 30w/w% ,1MP:GTA=7:3 , the concentration of doxycycline is 6w/w% .In addition , we found that the gel' s stickiness of PLGA75:25 is better than PLGA80:20' s.Integrate all these charactristics,we choose PLGA75:25 as the best formula . We add the rhBMP-2 to the gel .validate its activity by animal test.Section two Effect of sustained-release gel on experimental periodontitis of ratsIn order to validate the effect of sustained-release gel on periodontitis, the study do the reserch on periodontitis animal model of rats. We firstly created experimental animal mod...