微流控法制备可降解介孔生物玻璃载药栓塞微球

doi:10.15541/jim20260111

摘要/Abstract

摘要： 经动脉化疗栓塞术(TACE)是一种治疗不可切除肝肿瘤的常见临床干预手段, 但目前现有的栓塞微球在载药效率、药物缓释和力学性能适配等方面仍存在局限。为了解决上述问题, 本研究采用一步式微流控技术制备刚性介孔生物活性玻璃(MBG)微球, 其比表面积大、粒径尺寸均一可控, 介孔孔径在5和8 nm左右处呈现双峰分布, 且具有可降解性、高载药率和药物持续性缓释的特点。进一步地, 通过海藻酸钠(SA)包裹载阿霉素(DOX)的MBG微球, 构建了MBG-DOX@SA核壳结构复合微球, 实现了pH响应的药物缓释、控释效果。MBG-DOX@SA复合体系的药物包封率可达(81.50±1.93)%, SA壳层在栓塞初期便可阻止药物的爆发性释放, 并显著减缓累积释放率, 且在类肿瘤微环境的弱酸性(pH 5)条件下, 10 d后累计释放率仅达到(59.99±1.91)%。此外, SA的包覆增强了MBG-DOX微球的表面光滑度和弹性, 延长了药物扩散路径, 使得该复合微球在治疗过程中表现出更好生物安全性和栓塞效果的同时, 对肝肿瘤细胞的杀伤率仍能够维持在(36.00±0.03)%。这些结果表明MBG-DOX@SA微球在肝癌TACE领域具有很好的应用前景。

关键词: 介孔生物玻璃, 微球, 经动脉化疗栓塞术, 药物递送

Abstract: Transarterial chemoembolization (TACE) is a widely employed clinical procedure for the treatment of unresectable liver tumors. However, existing embolic microspheres exhibit certain limitations regarding drug loading capacity, sustained drug release, and mechanical adaptability. To address these challenges, in this study, the rigid mesoporous bioactive glass (MBG) microspheres via a one-step microfluidic technique were prepared, yielding particles with a high specific surface area, uniform and controllable size, bimodal pore size distribution with peaks at approximately 5 nm and 8 nm, as well as biodegradability, elevated drug loading efficiency, and sustained drug release profiles. Furthermore, doxorubicin (DOX)-loaded MBG microspheres were encapsulated within sodium alginate (SA) to form MBG-DOX@SA core-shell composite microspheres, which demonstrated pH-responsive and controlled drug release behavior. Drug encapsulation efficiency of this composite system was (81.50±1.93)%. SA shell effectively mitigated the initial burst release of the drug during early embolization and significantly decelerated the cumulative release rate. Under the weakly acidic conditions of the tumor microenvironment (pH 5), the cumulative release after 10 days was only (59.99±1.91)%. Additionally, the SA encapsulation enhanced the surface smoothness and elasticity of the DOX-loaded MBG microspheres, thereby extending the drug diffusion pathway, while also endowing the composite microspheres with improved biocompatibility and safety profiles during treatment. In antitumor tests, the composite microspheres achieved a cell death rate of (36.00±0.03)%. These results indicate that MBG-DOX@SA microspheres represent a promising candidate for application in TACE-based therapies for liver cancer.

Key words: mesoporous bioglass, microsphere, transarterial chemoembolization, drug delivery

中图分类号:

TQ174

张小亮, 杨子力, 田悦诚, 李得见, 朱敏. 微流控法制备可降解介孔生物玻璃载药栓塞微球[J]. 无机材料学报, DOI: 10.15541/jim20260111.

ZHANG Xiaoliang, YANG Zili, TIAN Yuecheng, LI Dejian, ZHU Min. Degradable Mesoporous Bioglass Microspheres for Chemoembolization Prepared by Microfluidic Method[J]. Journal of Inorganic Materials, DOI: 10.15541/jim20260111.

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