A Basic Study On New Anti-tuberculosis Tissue Engineering Bone

ObjectiveTo develop a kind of new anti-tuberculosis bone substitute and have a research on its physicochemical properties with a test of its drug release in vitro.MethodsThe first part, RFP-PLGA controlled release microspheres were prepared by emulsification-solvent evaporation method (O/W) and its morphology, particle size distribution, drug loading efficiency, encapsulation efficiency was analyzed to evaluate the preparation technology.Preliminary the drug release of the RFP-PLGA Ms in vitro was investigated, and its character of drug release was analyzed.The second part, divided into three groups:the first group was the pure calcium phosphate cement(CPC), namely group A, the second group(group B) was the CPC embedded with rifampicin(RFP-CPC), the third group was a complex with a combination of drug loaded PLGA microsphere and CPC, called as group C. The setting time, porosity was measured, then had a drug release test in vitro and the change of its compressive strength,fracture morphology and the drug release situation were observed after the strength test. ResultsThe first part:the particle size of the drug loaded microspheres were between100and150micrometer and had a sphere or ellipsoi dal shape with smooth surface. During the drug release test of the RFP-PLGA Ms, no significant drug burst appeared, and the cumulat ive release quantity accounted for92.31%with a steady and compl ete drug release process. Its drug release process had a fitting degr ee in pharmacokinetics of zero-order release, which showed that it locally released drug at a constant speed.1) The setting time:the pure CPC group had the shortest setting time, and the RFP-PLGA-CPC complex had the longest. Different groups had significant difference(F=49.23,P<0.01). But there was no significant difference between B and C(P>0.05). Both RFP-CPC and RFP-CPC-PLGA group were statistically significant, compared with the pure CPC group(P<0.01). Conclusion could be made that the drug and drug loaded microsphere made the setting time longer, however, the difference between the effect of drug loaded microsphere and drug to the setting time was minor.2) Porosity:we compared the calcium phosphate cement group with the RFP-CPC group,0.01<P<0.05, it showed a statistical difference. Both the pure CPC group and the RFP-CPC group had a significant difference with the group C(P<0.01). 3) The maximum compressive strength:the group C had a statistically difference with the pure CPC group(P<0.01). There was no statistically significant between group A and group B, however,it did have a significant difference as time goes by(3days:0.01<P<0.05,30days and60days:P<0.01). From the different groups and time spots with a further investigation, across the whole degradation of the material, the compressive strength of the CPC had not changed in a great deal, but both the RFP and RFP-PLGA MS had reduced the compressive strength at a certain degree.4) The scanning electron microscope(SEM):the size of the PLGA microspheres had a homogeneous size, between100-150um, with a sphere or ellipsoidal shape, smooth surface and no impuritie-s attached. The fracture section of the pure CPC had no obvious difference in PBS from the third day to the sixtieth day. The micro structure of the RFP-CPC group also had not changed too much with the micro particle fracture section, and we had no idea what the specific change of the drug in the CPC. The group C had a increase of small holes until the PLGA Ms disappeared(about60days), remaining empty holes, which showed the PLGA Ms had played a job as a porogen.5) The RFP-PLGA-CPC complex had no significant drug burst and the60days’ cumulative drug release rate had reached to95%. By linear fitting, the RFP-PLGA-CPC complex accorded with the pharmacokinetics of zero-order release format F=0.168*t, which im plied it released drug at a constant speed locally.ConclusionBase on the above findings, CPC imbedded with PLGA micros phere loaded with RFP could be used to cure bone tuberculosis an-dthis study would probably instruct the clinical application of the n ew sustained and controlled drug release material.