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| 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 |
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| DOI：10.3969/j.issn.1006-7108.2023.11.004 |
| 中文关键词: 骨代谢 骨靶向 口服递送 水凝胶微球 骨质疏松 |
| 英文关键词:bone metabolism bone-targeting oral delivery hydrogel microsphere osteoporosis |
| 基金项目: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） |
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| 中文摘要: |
| 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250.8 μm；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。 |
| 英文摘要: |
| 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 250.8 μm. Results of live/dead cell staining indicated that the micro/nano hydrogel microspheres had good biocompatibility. The Micro-CT and three-point bending test results 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 postmenopausal osteoporosis. |
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