不同剂量辛伐他汀载药体系对兔骨质疏松模型骨修复的实验研究

Study of the effect of a simvastatin drug delivery system on osteogenic activity in rat osteoporotic model

目的研发一种新型可注射、可降解及具有抗骨质疏松作用的载药缓释体系,观察其理化性能及对兔骨质疏松模型的骨修复效果。方法载药缓释体系以磷酸钙为基体,将载有不同剂量辛伐他汀(Simvastatin,SIM)的聚左乳酸(Poly-L-Lactic Acid,PLLA)微球与磷酸钙物理共混获得一种可注射、可降解及抗骨质疏松的载药体系,实验分为对照组、低剂量SIM-PLLA缓释组及高剂量SIM-PLLA缓释组,分别测定载药缓释体系的可注射性、凝固时间、力学强度、药物缓释规律及骨质疏松兔模型体内成骨活性。结果与对照组比较,含SIM-PLLA缓释体系凝固时间有所延长(P>0.05)、可注射性提高(P<0.05)且具有合适的抗压强度(P>0.05),植入骨质疏松兔体内4周及12周后,三组材料随着材料的降解均有新生骨长入,但SIM-PLLA缓释组材料的降解率及新骨生成率均显著优于对照组(P<0.05),其中以高剂量SIM-PLLA缓释组最高。结论 SIM-PLLA缓释体系具有良好的注射性能及合适的力学强度,对兔骨质疏松模型有明显的成骨活性及抗骨质疏松效果,有望成为治疗骨质疏松性椎体压缩骨折及不规则骨缺损的新型生物医学材料。

Objective To develop a novel multifunctional drug delivery system which is injectable and degradable with antiosteoporotic effect,and to evaluate its physical and chemical properties and osteogenic activity in a rabbit osteoporotic model.Methods A multifunctional drug delivery system was obtained by mixing different dosage of simvastatin（ SIM） microspheres with calcium phosphate biomaterial. The experiment was divided into simple calcium phosphate biomaterial group,lowdose SIM-PLLA drug delivery system group,and high dose SIM-PLLA drug delivery system group,respectively. The injectability,setting time,mechanical strength,and drug release property were determined to measure the material properties. In vivo osteogenic activity of the drug delivery system was estimated by implanting samples into a rabbit osteoporotic model. Results Compared with the calcium phosphate biomaterial group,the setting time in SIM- PLLA drug delivery system groups increased（ P〉0. 05）,and the injectability increased（ P〈0. 05） with appropriate compressive strength（ P〉0. 05）. After implantation into osteoporosis rabbits for4 weeks and 12 weeks,the degradation rate and the newbone formation rate in SIM-PLLA drug delivery groups were better than those in control group,and the best results achieved in high dose SIM-PLLA drug delivery system group（ P〈0. 05）. Conclusion SIM-PLLA drug delivery system has superior material properties with improved injectability, biodegradability, and proper mechanical strength. It shows clear osteogenic activity and anti-osteoporotic effect on rabbit osteoporosis model,which is expected to become a newbiomaterial for the treatment of osteoporotic vertebral compression fractures and irregular bone defect.