一种口服骨靶向微/纳水凝胶微球制备及对雌性去势小鼠骨质量影响的研究  

Preparation of an oral bone-targeting micro/nano hydrogel microsphere and its effect on bone quality in ovariectomized mice

作　　者：李俊杰 贾鹏[1] 刘功稳 张睿智 刘宝山 王爱飞[1] 徐又佳[1] LI Junjie;JIA Peng;LIU Gongwen;ZHANG Ruizhi;LIU Baoshan;WANG Aifei;XU Youjia(Department of Orthopedics,Osteoporosis Clinical Center,the Second Affiliated Hospital of Soochow University,Suzhou 215004,Jiangsu,China;Department of Orthopedics,Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine,Suzhou 215004,Jiangsu,China)

机构地区：[1]苏州大学附属第二医院骨科/骨质疏松症临床中心,江苏苏州215004 [2]南京中医药大学苏州附属医院骨伤科,江苏苏州215004

出　　处：《中国骨质疏松杂志》2023年第11期1581-1586,1597,共7页Chinese Journal of Osteoporosis

基　　金：国家重点研发计划(2021YFC2501700);国家自然科学基金面上项目(82072474);姑苏卫生人才计划(GSWS2020024);老年医学临床技术应用研究项目(LR2021022)。

摘　　要：目的制备新型口服骨靶向微/纳水凝胶微球,并了解其对雌性去势小鼠骨质量的影响。方法以多面体低聚倍半硅氧烷作为纳米平台,通过点击化学合成具有骨靶向性能的纳米颗粒,然后基于气体微流控和离子交联技术制备新型口服骨靶向微/纳水凝胶微球。采用活/死细胞染色评估微/纳水凝胶微球的生物相容性。选用18只8周龄雌性C57BL/6小鼠,随机分为去卵巢组(A组)、空白水凝胶微球组(B组)和微/纳水凝胶微球组(C组),每组6只。各组连续干预8周后收集小鼠股骨标本,采用微型计算机断层扫描(Micro-CT)分析骨小梁参数,利用三点弯曲测试评估股骨生物力学性能。结果骨靶向纳米颗粒具有均匀的球形形貌,平均粒径为40.6 nm;微/纳水凝胶微球呈球形形貌,表面粗糙,平均粒径为250.8μm;活/死细胞染色结果提示微/纳水凝胶微球具有良好的生物相容性。Micro-CT显示,C组小鼠的骨密度、骨体积分数、骨小梁数目均显著高于A组和B组小鼠,差异有统计学意义(P<0.05),C组小鼠的骨小梁间隙显著低于A组和B组小鼠,差异有统计学意义(P<0.05)。三点弯曲测试显示,C组小鼠的最大载荷和断裂能显著高于A组和B组小鼠,差异均有统计学意义(P<0.05)。结论新型口服骨靶向微/纳水凝胶微球具有良好的生物相容性,其负载的骨靶向纳米颗粒显著提高雌性去势小鼠骨质量,为绝经后骨质疏松症治疗提供了新的策略。Objective To prepare novel oral bone-targeting micro/nano hydrogel microspheres and to investigate their effects on bone quality in ovariectomized mice.Methods Polyhedral oligomeric silsesquioxane was used as a nanoplatform for the synthesis of bone-targeting nanoparticles by click chemistry,followed by the preparation of novel oral bone-targeting micro/nano hydrogel microspheres based on gas microfluidics and ionic cross-linking techniques.The biocompatibility of the micro/nano hydrogel microspheres was evaluated using live/dead cell staining.Eighteen 8-week-old female C57BL/6 mice were selected and randomly divided into ovariectomized group(group A),blank hydrogel microspheres group(group B),and micro/nano hydrogel microspheres group(group C).Following an 8-week period of continuous intervention,femoral samples from each group were collected.Bone trabecular parameters were analyzed using micro-computed tomography(Micro-CT).The biomechanical properties of the femur were evaluated using a three-point bending test.Results The bone-targeting nanoparticles had uniform spherical morphology with an average particle size of 40.6 nm.The micro/nano hydrogel microspheres had spherical morphology with a rough surface and an average particle size of 250.8μm.Results of live/dead cell staining indicated that the micro/nano hydrogel microspheres had good biocompatibility.The Micro-CT and three-point bending test result showed that bone mineral density,bone volume/total volume,trabecular number,maximum load,and fracture energy in group C were significantly higher than those in group A and B,with statistically significant differences(P<0.05).The trabecular separation in C group was significantly lower than that in group A and B,with statistically significant differences(P<0.05).Conclusion The novel oral bone-targeting micro/nano hydrogel microspheres have excellent biocompatibility.The loaded bone-targeting nanoparticles substantially improve bone quality in ovariectomized mice,providing a new strategy for the treatment of post

关 键 词：骨代谢 骨靶向 口服递送 水凝胶微球 骨质疏松 

分 类 号：R-332[医药卫生] R589