The Preliminary Reseach On Sustained Release System Of?-Cyclodextrin-Hollow Hydroxyapatite Composite Microspheres Loaded With Berberine

Backgroud: The preservation of vital pulp is essential for the treatment of dental pulp disease in young permanent teeth.The performance of ideal pulp capping agent is still the key in the preservation treatment of vital pulp.At present,calcium hydroxide is the main pulp capping agent in clinic,and mineral trioxide aggregate is used more and more widely,but there are some shortcomings,so it is of great significance to develop a new type of vital pulp preservation preparation which is more suitable for clinical needs.Studies have shown that berberine not only has anti-inflammatory and bacteriostatic effects,but also has the ability to promote the differentiation of dental pulp stem cells into dentin cells.Therefore,it can not only inhibit the occurrence of inflammation,kill the pathogenic bacteria for infected pulp,but also preserve pulp vitality and promote the differentiation of dental pulp stem cells to form the dentin bridge to promote the continued formation of tooth root.However,in order to control the sudden increase of drug concentration in blood,make the drug release continuously and promote the formation of dentin bridge fully to achieve therapeutic effect,it is necessary to find a suitable carrier to load the drug.At present,hollow hydroxyapatite microsphere synthesized by template method is one of the most common carriers of drug sustained release system.Adding ?-cyclodextrin to drug sustained release system can not only increase the drug loading efficiency and entrapment efficiency of berberine,but also slow down the sudden release,prolong the drug release time to give full effect,so as to apply it to pulp capping or active pulp preservation therapy.Objectives: By synthesizing ?-cyclodextrin-hydroxyapatite composite carrier with high drug loading efficiency and high encapsulation efficiency,a long local sustained-release system with no obvious sudden release of berberine was constructed to play an anti-inflammatory and bacteriostatic role,promote the differentiation of dental pulp stem cells into odontoblast,form dentin bridges in order to treat dental pulp diseases in children.Methods :(1)Calcium carbonate was synthesized with proline and sodium dodecyl sulfonate as template agent and converted into hollow carbon hydroxyapatite microspheres by hydrothermal precipitation.Berberine was dissolved in ?-cyclodextrin solution with different mass fractions to form inclusion compounds,which were loaded into hollow hydroxyapatite microspheres to construct a composite sustained-release system.The physicochemical properties of the synthesized hydroxyapatite microspheres and ?-cyclodextrin-hollow hydroxyapatite composite microspheres were characterized and analyzed by FESEM.(2)Prepare berberine-dimethyl sulfoxide solution,draw the standard curve of berberine,calculate the encapsulation efficiency and drug loading rate.(3)Compare the release of different mass fractions of ?-cyclodextrin composite microspheres loaded with berberine in vitro.Results :(1)Scanning electron microscope showed the "core�shell" complex structure of porous surface and hollow interior was synthesized.The diameter of the composite microspheres is 3-5 ?m and the wall thickness is 0.5-1?m.It was composed of short rod-like nanoparticles of 100�300 nm long.(2)When the mass fraction of ?-cyclodextrin carrier is 20%,the drug loading efficiency and encapsulation efficiency are the highest.(3)Release performance analysis in vitro showed that the synthesized ?-cyclodextrin-hollow hydroxyapatite composite microspheres loaded berberine released slowly in the early stage,delayed the sudden release,and the sustained release time reached 15 days,showing good sustained release performance.Conclusion:By dissolving berberine in ?-cyclodextrin solution with a certain mass fraction to form clathrate compound and loading the mixed solution into hollow hydroxyapatite microspheres,a local sustained-release system was successfully constructed.The encapsulation efficiency and drug loading rate of berberine loaded on the composite microspheres were improved,and the release in vitro showed good sustained-release performance.