目的 采用溶剂法制备负载迷迭香酸金属有机骨架纳米粒，并考察其体外性能。方法 通过单因素实验制备沸石咪唑酯骨架-8（ZIF-8）空白纳米粒，并采用正交试验优化制备了透明质酸修饰的迷迭香酸纳米粒（hyaluronic acid-modified rosmarinic acid nanoparticles，RZH）。并利用傅里叶变换红外光谱分析、热重分析等分析手段对RZH进行表征。采用透析法考察了载药系统的体外释药行为，对纳米粒进行体外抗氧化探究和溶血试验。结果 通过处方和工艺筛选，选择乙酸锌为锌源，10 min为最优反应时间，制备ZIF-8纳米粒。在此基础上，正交试验筛选最适投药量、药物与载体比例和透明质酸比例，制备出负载迷迭香酸的RZH纳米粒。外观形态、红外图谱和热重分析结果均表明成功制备了RZH。制备得到的RZH纳米粒粒径为（190.1±28.0）nm，ζ电位为（−18.6±0.8）mV，包封率为（90.75±1.53）%、载药量为（39.47±1.22）%。RZH纳米粒在pH 7.4的生理条件下表现出药物缓慢释放效果，48 h时的累积释放率超过60%，具有一定的缓释效果。此外，RZH对DPPH表现出浓度相关性的清除能力，清除率达到了97%以上。透明质酸修饰后的RZH溶血率显著降低，具有良好的血液相容性。结论 通过处方工艺的筛选制备得到载迷迭香酸的金属有机骨架纳米粒，载药量高，具有一定的缓慢释药行为、抗氧化能力和血液相容性，为迷迭香酸的医学应用提供了新思路。

Objective To prepare rosmarinic acid-loaded metal-organic framework nanoparticles by solvent method and investigate its properties in vitro. Methods Single factor test was used to prepare blank ZIF-8 nanoparticles, and hyaluronic acid-modified rosmarinic acid nanoparticles (RZH) were optimized and prepared through orthogonal experiments. The RZH was characterized by Fourier transform infrared spectroscopy and thermogravimetric analysis. The in vitro drug release behavior of the drug loading system was investigated by dialysis. The nanoparticles were subjected to in vitro antioxidant exploration and hemolysis test. Results ZIF-8 nanoparticles were prepared by selecting zinc acetate as the zinc source and 10 min as the optimal reaction time through prescription and process screening. And orthogonal experiments were conducted to screen the optimal drug amount, the ratio of drug to carrier, and the ratio of hyaluronic acid, and to prepare rosmarinic acid-loaded RZH nanoparticles. RZH was successfully prepared by characterization of the appearance morphology, infrared spectrum and thermogravimetric analysis. The particle size of RZH was (190.1 ± 28.0) nm, and the ζ potential was (−18.6 ± 0.8) mV. The encapsulation efficiency and drug loading were (90.75 ± 1.53)% and (39.47 ± 1.22)%, respectively. RZH nanoparticles exhibited a slow drug release effect under physiological conditions of pH 7.4, with a cumulative release rate exceeding 60% at 48 h, demonstrating a certain sustained release behavior. Moreover, RZH showed a concentration-dependent scavenging ability on DPPH with about 97%. Hyaluronic acid-modified RZH showed the lowest hemolysis and had good blood compatibility. Conclusion The rosmarinic acid-loaded metal-organic framework nanoparticles were successfully prepared through the prescription and process screening. The nanoparticles have high drug loading rate, slow drug release behavior, antioxidant capacity and blood compatibility, which provides a new idea for the medical application of rosmarinic acid.

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无锡市卫生健康委科研项目（M202323）；江苏高校青蓝工程项目（苏教师函[2024]14号）；江苏省生物质能源与材料重点实验室面上项目（JSBEM-S-202318）