摘要
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(rhIFN α-2b-SHCMM),研究结果为后期离子交换载药提供了可行性.
Abstract
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 interferon α-2b crosslinked mesoporous microspheres(rhIFN α-2b-SHCMM)was achieved,demonstrating both high entrapment efficiency and an enhanced drug loading capacity.
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