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酶/磁双驱动果胶/海藻酸钠复合微球的制备及表征

Preparation and Characterization of Enzyme/Magnetic-driven Pectin/Sodium Alginate Composite Microsphere

  • 摘要: 设计构建了酶/磁双驱动的果胶(PET)/海藻酸钠(SA)复合微球机器人药物递送系统,即通过注滴法,以乳酸钙为交联剂,将Fe3O4磁性纳米粒子(Mag)、过氧化氢酶(CAT)/葡萄糖氧化酶(GOD)/磷酸锌杂合颗粒、天然喜树碱衍生物(盐酸伊立替康CPT-11)药物同时装载到PET/SA复合微球中,制备得到磁响应的负载双酶驱动载药磷酸锌杂合颗粒的PET/SA复合微球(CPT-11/CAT/GOD-Zn3(PO4)2@Mag/PET-SA)。考察了不同PET与SA复配比及磁性颗粒的加入对复合微球结构、形貌、粒径及药物包封率的影响,采用UV-vis法测定了载药微球机器人在模拟胃液(SGF,pH值1.2)和模拟肠液(SIF,pH值6.8)释放介质中的药物释放曲线。研究结果表明:制备得到的酶/磁双驱动微球载药机器人球形度好,但磁性颗粒的加入使复合微球表面出现大量褶皱,变得粗糙,从而使药物包封率有明显的下降;当m(PET)∶m(SA)为1∶3时,加入磁性颗粒前复合微球的平均粒径为1.658 mm,包封率为63.1%,加入磁性颗粒后复合微球的平均粒径增加至1.885 mm,包封率下降至47.7%;在SGF中盐酸伊立替康药物的释放较为缓慢,而在SIF中快速释放;振动样品磁强计(VSM)测试表明该复合微球具有超顺磁性和高磁化强度,并且在葡萄糖溶液中可以进行自驱动。

     

    Abstract: This study designed and constructed an enzyme/magnetic dual-driven pectin(PET)/sodium alginate(SA) composite microsphere robot drug delivery system. Specifically, through the dropwise method, calcium lactate was used as a crosslinking agent to simultaneously load Fe3KG-*6O4 magnetic nanoparticles(Mag), catalase(CAT)/glucose oxidase(GOD)/zinc phosphate hybrid particles, and a natural camptothecin derivative(irinotecan hydrochloride CPT-11) drug into PET/SA composite microspheres, by which fabricated the magnetically responsive PET/SA composite microspheres(CPT-11/CAT/GOD-Zn3(PO4)2@Mag/PET-SA). The effects of different compounding ratios of PET to SA and the addition of magnetic particles on the structure, morphology, particle size, and drug encapsulation efficiency of the composite microspheres were investigated. The drug release curves of the drug-loaded microsphere robots in simulated gastric fluid(SGF, pH value 1.2) and simulated intestinal fluid(SIF, pH value 6.8) were determined by ultraviolet spectrometry method. The results showed that the prepared enzyme/magnetic dual-driven microsphere drug-loading robot had good sphericity, but the addition of magnetic particles caused the appearance of a lot of wrinkles and become rough on the surface of the composite microspheres, leading to a significant decrease in drug encapsulation rate. When the ratio of m(PET) to m(SA) was 1∶3, the average particle size of the composite microspheres before the addition of magnetic particles was 1.658 mm, with an encapsulation rate of 63.1%. After the addition of magnetic particles, the average particle size of the composite microspheres increased up to 1.885 mm, and the encapsulation rate decreased up to 47.7%. The release of irinotecan hydrochloride drug was relatively slow in SGF while it released rapidly in SIF. Vibrating sample magnetometer(VSM) tests indicated that the composite microspheres exhibited superparamagnetism and high magnetization intensity, and could undergo self-driven in a glucose solution.

     

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