Synthesis of mesoporous sodium hyaluronate microspheres via electrostatic spray method  

静电喷雾法制备透明质酸钠介孔微球

作　　者：Wei Huang Jie Zhu Yingshu Feng Dan Yang Caleb Kesse Firempong Yang Qu Haibing He Hongfei Liu 黄维;朱洁;冯颖淑;杨丹;Caleb Kesse Firempong;屈阳;何海冰;刘宏飞(江苏大学药学院,江苏镇江212013;江苏苏南药业工业有限公司,江苏镇江212400;镇江医学院医学化学研究所,镇江市功能化学重点实验室,江苏镇江212028;扬子江药业集团南京海陵药业有限公司,江苏南京210046;江苏海之宏生物医药有限公司,江苏南通226001)

机构地区：[1]College of Pharmacy,Jiangsu University,Zhenjiang 212013,Jiangsu,China [2]Jiangsu Sunan Pharmaceutical Industrial Co.,LTD,Zhenjiang 212400,Jiangsu,China [3]Zhenjiang Key Laboratory of Functional Chemistry,Institute of Medicine&Chemical Engineering,Zhenjiang College,Zhenjiang 212028,Jiangsu,China [4]Yangtze River Pharmaceutical Group Nanjing Hailing Pharmaceutical Company,Nanjing 210046,Jiangsu,China [5]Jiangsu Haizhihong Biomedical Co.,Ltd,Nantong 226001,Jiangsu,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2024年第11期985-1000,共16页中国药学（英文版）

基　　金：The 2023 Nantong Social Livelihood Science and Technology Plan;2023 Nantong Jianghai Talents Project;2022 New Drugs and Platform Enhancement Project of the Yangtze Delta Drug Advanced Research Institute. Zhenjiang Science and Technology Pro ject (Grant No. SH2020048);China Postdoctoral Science Foundation (Gr ant No. 2020M681532);Jiangsu Planned Projects for Postdoctoral Research Funds (Grant No. 2020Z209);Natural Science Research Pro jects of Universities in Jiangsu Province (Grant No. 20KJD350001)。

摘　　要：In the present study,we employed electrostatic spray technology to fabricate mesoporous microspheres containing sodium hyaluronate(SHMM).This approach aimed to overcome a significant challenge in the formulation development process,specifically addressing the limited water-locking ability inherent to the double-helix structure of sodium hyaluronate(SH).Various parameters were systematically investigated,including the solvent employed,concentrations of SH and poly(ethylene oxide),electrospray flow rate,voltage settings,and needle diameter.Through systematic single-factor testing,we identified the optimal formulation process for generating SH microspheres characterized by favorable morphology and particle size.Additionally,a similar single-factor examination focused on the concentration of the pore-forming agent and the drying temperature,leading to the successful production of mesoporous microspheres with discernible pores.The porosity of the three distinct batches of mesoporous microspheres was consistently measured at 20.30%±1.51%.Moreover,all these microspheres displayed a negative surface potential when suspended in water,affirming their strong capacity to bind with positively charged protein drugs.These findings underscored the feasibility of drug loading through ion exchange in subsequent stages.Notably,the successful preparation of recombinant human interferonα-2b crosslinked mesoporous microspheres(rhIFNα-2b-SHCMM)was achieved,demonstrating both high entrapment efficiency and an enhanced drug loading capacity.本研究采用静电喷雾技术制备透明质酸钠介孔微球(SHMM),解决了配方开发过程中透明质酸钠(SH)双螺旋结构的锁水能力问题。本文采用单因素试验对溶剂类型、SH和聚环氧乙烷浓度、流速、电喷雾电压和针头直径等因素进行了考察,获得了透明质酸钠微球的最佳处方工艺,制备出了形貌和粒径均较好的微球。同时采用单因素试验对致孔剂浓度和干燥温度进行了评价,制备出了具有明显孔结构的介孔微球。3批介孔微球的孔隙率为2.30%±1.51%,在水中均表现出负电位,证明其具有良好的结合带正电蛋白药物的能力。本文成功制备了包封率高、载药量高的重组人干扰素α-2b交联介孔微球(rhIFNα-2b-SHCMM),研究结果为后期离子交换载药提供了可行性。

关 键 词：Electrostatic spray Ion exchange technology Sodium hyaluronate mesoporous microspheres 

分 类 号：R943[医药卫生—药剂学]