Local Controlled Release Preparation And Performance Analysis Of Anti Osteoporosis Drug Microspheres

With the aging society, osteoporosis becomes more and more attentions, and osteoporotic fracture is the most destructive complications of osteoporosis, the first risk of fracture and secondary fracture patients in the next few years increased 3-5 times, also has a high morbidity and mortality, not only greatly reduces the the quality of life of patients, but also caused great burden to the family and society. Osteoporotic fracture in the treatment is different from the conventional fracture, the routine operation of the fracture site was reset, can not solve the osteoporosis bone density decrease this fundamental reason fundamentally. Osteoporosis treatment prior is to enhance the bone density in different ways, and osteoporotic fractures in a common site for the spine, hip and distal forearm, conventional anti osteoporosis treatment can not achieve on the easy fracture sites focus on purpose. In order to focus on osteoporosis easily reached the fracture position, we use PLGA as the carrier material, the alendronate sodium as a carrier of drug, the use of rapid membrane emulsification combined with W/O/W method, synthetic drug loaded microspheres, by injection mode, to achieve on osteoporosis fracture site to easily focused treatment.The use of rapid membrane emulsification combined with W/O/W method for preparation of drug loaded microspheres, and observe the drug loaded microspheres particle size, electron microscope, the entrapment efficiency of drug loaded microspheres and the drug loading rate measurement, measuring the effects of sustained release drug loaded microspheres in vitro environment.The drug loaded microspheres implantation in vivo in rats, observe the local tissue compatibility, through the drug loaded microspheres dissolved in saline, rats were injected through tail vein, observation of rat liver, kidney, heart, lung and other large tissue biocompatibility.50 female SD rats were randomly divided into 5 groups, 10 rats in group A, sham operation group, B group, C group, D group, E group with 10 rats in each group, through the operation of ovariectomy, osteoporosis model. After 8 weeks, the A group compared with B, C, from D, in group E, 10 rats were randomly selected for the left mid thigh bone density detection, detection of osteoporosis modeling results. After the success of modeling, B group as the osteoporosis group, without any intervention; group C as systemic administration group, administered by gavage; D group was the blank microspheres group, through the injection of microspheres underwent left mid thigh injection; group E microspheres group, through the injection side to left the Mid Thigh injected microspheres. After 8 weeks, all the rats were sacrificed, take the left femur, the E group at the same time take right femur were measured in rats, left leg bone density measurement, and left, right leg bone density in E group. At the same time the rats left femur bone stress were measured and compared, and the rats of group E left and right sides femoral stress measurement.Through the rapid membrane emulsification combined with drug loaded microspheres prepared by W/O/W method, is a kind of white powder, particle size uniformity, electron microscope observation, full, uniform particle size. The actual measurement of the drug loaded microspheres drug loading rate is(2.74±0.16)%; the actual encapsulation rate was(71.15±4.27)%. In vitro release test proved that the drug loaded microspheres in vitro, the first effect 24 hours, then released more stable, continuous measurements of 16 days, the drug loaded microspheres in vitro release rate reached about 90%.Local tissue drug loaded microspheres compatibility test proved that the drug loaded microspheres local tissue describe tissue surrounding the better, there is no obvious inflammatory reaction, biopsy showed no obvious local inflammatory cell infiltration. Liver, kidney, lung, heart and other large tissue compatibility test results prove that, the local no obvious deformation and necrosis, the pathological sections showed no significant difference with normal tissue.After 8 weeks, bone density detection, comparison between the P<0.05 group, it was proved that the model is successful. The rats in each group were different after 8 weeks of treatment, detection of bone density results suggest: B, C, D, E group of left femur bone density was significantly lower than that of A group, the comparison between P<0.05 group; group C, E group than in B group, bone density increased, the comparison between the P<0.05 group; D group compared with B group bone mineral density had no obvious change, compared P>0.05 group; E group compared with C group, the bone density increased significantly, P<0.05. The rats in group E bilateral femoral bone mineral density around P<0.05. Femoral stress test results suggest that: B, C, D, E group of left femur of three point bend maximum load value decreased obviously compared with A group, the comparison between P<0.05 group; group C, E group than in B group of three point bend maximum load values were significantly increased, compared P<0.05 group; D group of three point bend maximum load value compared with B group, no significant difference between P>0.05 group, E group and C group; comparison of three point bend maximum load was increased, P<0.05. The rats in group E bilateral femoral stress test results P<0.05.In summary, application of rapid membrane emulsification combined with W/O/W method, can drug loaded microspheres preparation of uniform particle size, and has good encapsulation rate of drug loading rate, the in vitro experiment proved that the first 24 hours with a burst effect, the rest of the time release is steady, the 16 day drug release rate can reach to about 90%. Rats in vivo tests prove that the microspheres have good histocompatibility, and no obvious side effects on the liver, kidneys, heart, lungs and other organs. Through the model rats compared with sham operation group, prove the osteoporosis rat model success. Through the different modalities of therapy, drug loaded microspheres after local application of proof, local bone density is significantly greater than the systemic medication group, and the bone stress than systemic administration group had significant improvement.Prove that the drug loaded microspheres of local application of anti osteoporosis drug package can be applied to the fracture site to achieve local key release treatment.