中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (26): 6840-6848.doi: 10.12307/2026.761

• 材料生物相容性 material biocompatibility • 上一篇    下一篇

奥当卡替载药微球-凝胶复合缓释载体的制备及生物相容性

吕天阳1，李  宁1，黄  硕2，刘昌奎2，郭亚媛2，3，胡开进1，2，3   

  1. 1锦州医科大学口腔医学院，辽宁省锦州市  121000；2西安医学院口腔医学院西安市口颌系统疾病防治重点实验室，陕西省西安市  710021；3西安医学院第三附属医院，陕西省西安市  710065
  • 接受日期:2025-09-30 出版日期:2026-09-18 发布日期:2026-03-12
  • 通讯作者: 郭亚媛，博士，讲师，西安医学院口腔医学院西安市口颌系统疾病防治重点实验室，陕西省西安市 710021；西安医学院第三附属医院，陕西省西安市 710065 胡开进，博士生导师，主任医师，锦州医科大学口腔医学院，辽宁省锦州市 121000；西安医学院口腔医学院西安市口颌系统疾病防治重点实验室，陕西省西安市 710021；西安医学院第三附属医院，陕西省西安市 710065
  • 作者简介:吕天阳，男，1999年生，山东省济南市人，汉族，在读硕士，主要从事牙槽骨缺损修复材料研发工作。
  • 基金资助:
    陕西省科技厅重点研发一般项目(2024SF-YBXM-434)，项目负责人：胡开进；西安科技局重大专项项目(23LLRHZDZX0010)，项目负责人：胡开进；陕西省教育厅重点项目-高校工程研究中心项目(24JR145)，项目负责人：黄硕；陕西省科技厅自然科学基础研究项目(2025JC-YBQN-1274)，项目负责人：郭亚媛

Preparation and biocompatibility of odanacatib microspheres-gel composite sustained-release carrier 

Lyu Tianyang1, Li Ning1, Huang Shuo2, Liu Changkui2, Guo Yayuan2, 3, Hu Kaijin1, 2, 3   

  1. 1School of Stomatology, Jinzhou Medical University, Jinzhou 121000, Liaoning Province, China; 2Xian Key Laboratory for the Prevention and Control of Stomatognathic System Disorders, School of Stomatology of Xi’an Medical University, Xi’an 710021, Shaanxi Province, China; 3The Third Affiliated Hospital, Xi’an Medical University, Xi’an 710065, Shaanxi Province, China
  • Accepted:2025-09-30 Online:2026-09-18 Published:2026-03-12
  • Contact: Guo Yayuan, MD, Lecturer, Xian Key Laboratory for the Prevention and Control of Stomatognathic System Disorders, School of Stomatology of Xi’an Medical University, Xi’an 710021, Shaanxi Province, China; The Third Affiliated Hospital, Xi’an Medical University, Xi’an 710065, Shaanxi Province, China Hu Kaijin, Doctoral supervisor, Chief physician, School of Stomatology, Jinzhou Medical University, Jinzhou 121000, Liaoning Province, China; Xian Key Laboratory for the Prevention and Control of Stomatognathic System Disorders, School of Stomatology of Xi’an Medical University, Xi’an 710021, Shaanxi Province, China; The Third Affiliated Hospital, Xi’an Medical University, Xi’an 710065, Shaanxi Province, China
  • About author:Lyu Tianyang, MS candidate, School of Stomatology, Jinzhou Medical University, Jinzhou 121000, Liaoning Province, China
  • Supported by:
    Key R&D Project of Shaanxi Provincial Department of Science and Technology, No. 2024SF-YBXM-434 (to HKJ); Major Project of Xi’an Science and Technology Bureau, No. 23LLRHZDZX0010 (to HKJ); Shaanxi Provincial Department of Education Key Project - University Engineering Research Center Project, No. 24JR145 (to HS); Basic Research Project of Natural Science of Shaanxi Provincial Department of Science and Technology, No. 2025JC-YBQN-1274 (to GYY)

PDF

13

摘要：

文题释义：
奥当卡替：是一种选择性组织蛋白酶K抑制剂，通过抑制蛋白酶活性减少破骨细胞对骨基质的降解，有助于增加骨密度。奥当卡替能够促进M2型巨噬细胞极化，发挥抗炎作用。
载药微球：作为一种将药物包裹或吸附在微米级球状载体中的药物递送系统，具有延缓药物释放时间、促进药物靶向递送并保护药物活性的重要作用。

背景：奥当卡替能有效发挥抗炎作用，促进牙周炎缺损区域牙槽骨修复，但是需要多次注射药液来保证疗效，操作繁琐。
目的：制备奥当卡替载药微球-凝胶复合缓释载体，表征该载体的生物相容性。
方法：①通过乳化-溶剂挥发法制备负载不同质量奥当卡替的聚乳酸-羟基乙酸共聚物微球(记为ODN-MS)，通过载药量与包封率检测选择5 mg奥当卡替与40 mg聚乳酸-羟基乙酸共聚物制备的微球进行后续实验。将不同质量的ODN-MS与甲基丙烯酰化明胶溶液混合制备凝胶复合缓释载体(记为ODN-MS-Gel)，其中ODN-MS的质量浓度分别为250，500 μg/mL。表征ODN-MS、250 μg/mL ODN-MS-Gel的微观形貌、体外药物释放性能。②分别采用甲基丙烯酰化明胶凝胶浸提液、负载聚乳酸-羟基乙酸共聚物微球的凝胶复合缓释载体浸提液及250，500 μg/mL ODN-MS-Gel浸提液培养兔骨髓间充质干细胞，CCK-8法检测细胞增殖。分别采用甲基丙烯酰化明胶凝胶浸提液、负载聚乳酸-羟基乙酸共聚物微球的凝胶复合缓释载体浸提液及250 μg/mL ODN-MS-Gel浸提液培养兔骨髓间充质干细胞，活/死染色检测细胞活力。将兔骨髓间充质干细胞分别接种于甲基丙烯酰化明胶凝胶、负载聚乳酸-羟基乙酸共聚物微球的凝胶复合缓释载体与250 μg/mL ODN-MS-Gel上，鬼笔环肽染色与扫描电镜观察细胞黏附情况。 
结果与结论：①光学显微镜下可见ODN-MS呈球型，均匀分布且无团聚现象。扫描电镜下可见ODN-MS表面呈现细小的多孔结构；250 μg/mL ODN-MS-Gel水凝胶呈多孔结构，并且ODN-MS分布于水凝胶的多孔结构中。ODN-MS和250 μg/mL ODN-MS-Gel均能够实现药物缓释作用，并且250 μg/mL ODN-MS-Gel体系药物释放较平缓，实现双重缓释效果。②CCK-8检测显示，250，500 μg/mL ODN-MS-Gel浸提液可促进兔骨髓间充质干细胞的增殖。活/死染色显示，250 μg/mL ODN-MS-Gel浸提液不影响兔骨髓间充质干细胞的活力。鬼笔环肽染色与扫描电镜观察显示，相较于其他两种材料，250 μg/mL ODN-MS-Gel可促进兔骨髓间充质干细胞的黏附。结果表明，ODN-MS-Gel能够实现奥当卡替的持续缓释，并且具有良好的生物相容性。
https://orcid.org/0009-0004-0264-5125(吕天阳)

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料；口腔生物材料；纳米材料；缓释材料；材料相容性；组织工程

关键词: 奥当卡替, 聚乳酸-羟基乙酸共聚物微球, 甲基丙烯酰化明胶, 药物缓释, 生物相容性, 牙周炎

Abstract: BACKGROUND: Odanacatib effectively exerts anti-inflammatory effects and promotes alveolar bone repair in periodontitis-affected areas. However, multiple injections are required to ensure efficacy, which is cumbersome. 
OBJECTIVE: To prepare an odanacatib-loaded microsphere-gel composite sustained-release carrier and characterize its biocompatibility.  
METHODS: (1) Poly(lactic-co-glycolic acid) microspheres (ODN-MS) loaded with varying amounts of odanacatib were prepared by an emulsification-solvent evaporation method. Microspheres prepared with 5 mg of odanacatib and 40 mg of poly(lactic-co-glycolic acid) were selected for subsequent experiments based on drug loading and encapsulation efficiency. A gel composite sustained-release carrier (ODN-MS-Gel) was prepared by mixing varying amounts of ODN-MS with a gelatin methacryloyl solution. The ODN-MS mass concentrations were 250 and 500 μg/mL, respectively. The micromorphology and in vitro drug release properties of the ODN-MS and 250 μg/mL ODN-MS-Gel were characterized. (2) Rabbit bone marrow mesenchymal stem cells were cultured using extracts of gelatin methacryloyl gel, extracts of a composite sustained-release carrier loaded with poly(lactic-co-glycolic acid) microspheres, and extracts of 250 and 500 μg/mL ODN-MS-Gel, respectively. Cell proliferation was assessed by CCK-8 assay. Rabbit bone marrow mesenchymal stem cells were cultured using extracts of gelatin methacryloyl gel, extracts of a composite sustained-release carrier loaded with poly(lactic-co-glycolic acid) microspheres, and extracts of 250 μg/mL ODN-MS-Gel, respectively. Cell viability was assessed by live/dead staining. Rabbit bone marrow mesenchymal stem cells were seeded onto gelatin methacryloyl gel, a composite sustained-release carrier loaded with poly(lactic-co-glycolic acid) microspheres, and 250 μg/mL ODN-MS-Gel, respectively. Cell adhesion was observed by phalloidin staining and scanning electron microscopy.
RESULTS AND CONCLUSION: (1) Optical microscopy revealed that the ODN-MS was spherical, uniformly distributed, and free of agglomerates. Scanning electron microscopy revealed a fine porous structure on the surface of ODN-MS. The 250 μg/mL ODN-MS-Gel hydrogel exhibited a porous structure, with ODN-MS distributed throughout the hydrogel's porous structure. Both ODN-MS and 250 μg/mL ODN-MS-Gel achieved sustained drug release, with the 250 μg/mL ODN-MS-Gel system exhibiting a more gradual release, demonstrating a dual sustained-release effect. (2) CCK-8 assay revealed that the 250 and 500 μg/mL ODN-MS-Gel extracts promoted the proliferation of rabbit bone marrow mesenchymal stem cells. Live/dead staining revealed that the 250 μg/mL ODN-MS-Gel extract did not affect the viability of rabbit bone marrow mesenchymal stem cells. Phalloidin staining and scanning electron microscopy revealed that the 250 μg/mL ODN-MS-Gel promoted the adhesion of rabbit bone marrow mesenchymal stem cells compared with the other two materials. The results verify that ODN-MS-Gel can achieve sustained release of odanacatib and has good biocompatibility.

Key words: odanacatib, poly(lactide-co-glycolic acid) microsphere, gelatin methacryloyl, drug sustained release, biocompatibility, periodontitis

中图分类号: