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幽门螺杆菌重组蛋白PLGA微球和PLGA-壳聚糖复合微球的制备及其释放性能研究

陈昱作 刘人捷 杨露 李茂圆 索朗斯珠 李婉宜 王保宁

陈昱作, 刘人捷, 杨露, 等. 幽门螺杆菌重组蛋白PLGA微球和PLGA-壳聚糖复合微球的制备及其释放性能研究[J]. 四川大学学报(医学版), 2021, 52(5): 794-798. doi: 10.12182/20210960208
引用本文: 陈昱作, 刘人捷, 杨露, 等. 幽门螺杆菌重组蛋白PLGA微球和PLGA-壳聚糖复合微球的制备及其释放性能研究[J]. 四川大学学报(医学版), 2021, 52(5): 794-798. doi: 10.12182/20210960208
CHEN Yu-zuo, LIU Ren-jie, YANG Lu, et al. Preparation and Release Properties of Helicobacter pylori Recombinant Protein PLGA Microspheres and PLGA-Chitosan Microspheres[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(5): 794-798. doi: 10.12182/20210960208
Citation: CHEN Yu-zuo, LIU Ren-jie, YANG Lu, et al. Preparation and Release Properties of Helicobacter pylori Recombinant Protein PLGA Microspheres and PLGA-Chitosan Microspheres[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(5): 794-798. doi: 10.12182/20210960208

幽门螺杆菌重组蛋白PLGA微球和PLGA-壳聚糖复合微球的制备及其释放性能研究

doi: 10.12182/20210960208
基金项目: 四川省科技厅重点研发项目(No. 21ZDYF1885、No. 2021YFS0054),成都市科技局项目(No. 2019-YF05-00298-SN)和西藏农牧学院柔性引进人才项目(No. RXYJ1905)资助
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Preparation and Release Properties of Helicobacter pylori Recombinant Protein PLGA Microspheres and PLGA-Chitosan Microspheres

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  • 摘要:   目的  制备载有幽门螺杆菌重组蛋白(BIB蛋白)的聚乳酸-羟基乙酸共聚物(poly lactic-co-glycolic acid, PLGA)微球和PLGA-壳聚糖复合微球,优化微球制备参数,并分析两种微球在体外胃、肠液中的释放性能。  方法  采用双乳化-溶剂挥发法(W1/O/W2)制备BIB-PLGA微球和BIB-PLGA-壳聚糖复合微球;通过单因素分析方法,研究水相/油相(W1/O)比例、PLGA质量分数、聚乙烯醇(polyvinyl alcohol, PVA)浓度等对微球外观、粒径、分散指数(polydispersity index, PDI)、包封率和载药率的影响,确定最优参数,采用BCA法测定蛋白浓度,计算微球累计释放率。  结果  本研究的最佳参数条件为:W1/O为1∶2,PLGA质量分数5%,PVA质量分数0.2%。BIB-PLGA微球包封率(78.20±1.73)%,载药率(10.58±0.23)%,粒径(2.11±0.08) μm,PDI(0.35±0.18);BIB-PLGA-壳聚糖复合微球包封率(78.87±1.30)%,载药率(15.50±0.25)%,粒径(2.28±0.52) μm,PDI(0.39±0.54)。BIB-PLGA微球和BIB-PLGA-壳聚糖复合微球在体外胃、肠液中均能缓慢释放,BIB-PLGA-壳聚糖复合微球的缓释效果更明显。  结论  采用双乳化-溶剂挥发法制备的BIB-PLGA微球和BIB-PLGA-壳聚糖复合微球载药率和包封率都较高,粒径可控,外观分散,对胃肠液有缓释作用。
  • 图  1  微球透射电镜图

    Figure  1.  Transmission electron microscope images of microspheres

    A: Oil phase was 5% PLGA, external water phase was 0.2% PVA, and W1/O was 1∶2; B: Oil phase was 5% PLGA, external water phase was 0.2% PVA, W1/O was 1∶2, and chitosan was 1% .

    图  2  微球在体外胃肠液中的释放曲线

    Figure  2.  Release curves of microspheres in gastric and intestinal fluids in vitro

    A: Release curves of microspheres in gastric fluids in vitro; B: Release curves of microspheres in intestinal fluids in vitro. *P<0.05, vs. BIB-PLGA. n=3.

    表  1  不同内水相和油相(W1/O)体积比BIB-PLGA微球的理化性能

    Table  1.   Physicochemical properties of BIB-PLGA microspheres prepared under different W1/O volume-by-volume ratios

    W1/O(V/VParticle size/μmPDIEE/%DL/%
    2∶1 2.39±0.32 0.43±0.50 69.42±1.56 49.36±1.11
    1∶1 2.36±0.41 0.41±0.38 69.20±0.85 31.34±0.39
    1∶2 2.31±0.37 0.37±0.05 80.04±0.60 22.26±0.17
    1∶3 1.82±0.15 0.56±0.36 69.93±1.46 13.04±0.27
    1∶4 0.87±0.04 0.40±0.52 70.33±6.85 10.47±1.02
     PDI: Polydispersity index; EE: Encapsulation efficiency; DL: Drug loading. n=3.
    下载: 导出CSV

    表  2  不同PLGA的质量分数下BIB-PLGA微球的理化性能

    Table  2.   Physicochemical properties of microspheres prepared under different PLGA mass fractions

    PLGA/%Particle size/μmPDIEE/%DL/%
    2 2.31±0.37 0.37±0.05 80.04±0.60 22.26±0.17
    3 2.07±0.15 0.48±0.45 79.75±2.28 15.89±0.17
    4 3.13±0.72 0.60±0.35 82.90±0.70 13.10±0.11
    5 2.74±0.38 0.44±0.30 87.50±3.02 11.42±0.39
     PLGA: Poly lactic-co-glycolic acid; PDI: Polydispersity index; EE: Encapsulation efficiency; DL: Drug loading. n=3.
    下载: 导出CSV

    表  3  不同质量分数PVA下BIB-PLGA微球的理化性能

    Table  3.   Physicochemical properties of microspheres prepared under different PVA mass fractions

    PVA/%Particle size/μmPDIEE/%DL/%
    0.2 2.11±0.08 0.35±0.18 78.20±1.73 10.58±0.23
    0.4 2.45±0.54 0.52±0.18 82.01±0.98 10.55±0.13
    0.8 2.55±0.12 0.50±0.33 86.22±1.36 10.39±0.16
    1.6 2.74±0.38 0.44±0.30 87.50±3.02 11.42±0.39
     PVA: Polyvinyl alcohol; PDI: Polydispersity index; EE: Encapsulation Efficiency; DL: Drug loading. n=3.
    下载: 导出CSV

    表  4  BIB-PLGA微球、BIB-PLGA-壳聚糖复合微球的理化性能

    Table  4.   Physicochemical properties of BIB-PLGA and BIB-PLGA-chitosan microspheres prepared

    Microspheres W1/OPLGA/%PVA/%Chitosan/%Particle size/μmPDIEE/%DL/%
    BIB-PLGA 1∶2 5 0.2 2.11±0.08 0.35±0.18 78.20±1.73 10.58±0.23
    BIB-PLGA-CS 1∶2 5 0.2 1 2.28±0.52 0.39±0.54 78.87±1.30 15.50±0.25
     PVA: Polyvinyl alcohol; PLGA: Poly lactic-co-glycolic acid; PDI: Polydispersity index; EE: Encapsulation efficiency; DL: Drug loading. n=3.
    下载: 导出CSV
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出版历程
  • 收稿日期:  2020-10-12
  • 修回日期:  2021-09-02
  • 网络出版日期:  2021-12-06
  • 刊出日期:  2021-09-20

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