Preparation of Protein-Loaded Poly(L-Lactide) Microspheres by Solution-Enhanced Dispersion by Supercritical CO2

A. Chen, C. Zhao, Shi-Bin Wang, Yuangang Liu
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Abstract

SiO2-hemoglobin-poly(L-lactide) (SiO2-Hb-PLLA) microspheres were prepared in a process of solution-enhanced dispersion by supercritical CO2 (SEDS). SiO2 nanoparticles were loaded with Hb by adsorption firstly and then the Hb-SiO2 nanoparticles were further coated with PLLA by the SEDS process. The resulted microcapsules were characterized by scanning electron microscope (SEM), laser diffraction particle size analyser and Fourier transform infrared spectrometer (FTIR). The drug release profiles were also determined. The Hb-SiO2-PLLA microspheres have a narrow particle size distribution (PDI 0.189) with a mean particle size of 897nm and a drug loading of 7.1%. After coating with PLLA, the drug release from SiO2-Hb-PLLA showed a sustained process mainly in zero-order kinetics; only 3.7% drug was released in the first 24 hours, versus 51.9% for those without coating, which revealed that the coating of PLLA significantly retarded the drug release. The results also indicate that the SEDS process is a typical physical process to produce protein-loaded polymer microspheres without changing the molecular structure of proteins, which is potential in the application of designing proteins drug delivery system.
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超临界CO2溶液增强分散法制备载蛋白聚l -丙交酯微球
采用超临界CO2溶液增强分散法制备了sio2 -血红蛋白-聚l -丙交酯(SiO2-Hb-PLLA)微球。通过吸附将Hb负载在SiO2纳米颗粒上,然后用SEDS法将Hb-SiO2纳米颗粒包被PLLA。采用扫描电镜(SEM)、激光衍射粒度分析仪和傅里叶变换红外光谱仪(FTIR)对制备的微胶囊进行了表征。同时测定了药物释放谱。制备的Hb-SiO2-PLLA微球粒径分布窄(PDI为0.189),平均粒径为897nm,载药量为7.1%。包被PLLA后,药物从SiO2-Hb-PLLA中释放的过程以零级动力学为主;前24 h药物释放率为3.7%,未包衣组为51.9%,说明PLLA包衣显著延缓了药物释放。结果还表明,SEDS工艺是一种在不改变蛋白质分子结构的情况下制备载蛋白聚合物微球的典型物理工艺,在设计蛋白质给药系统方面具有应用潜力。
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