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  • ISSN 1006-3080
  • CN 31-1691/TQ

聚合物前药载药性能的计算机模拟

罗雪莉 郎美东

罗雪莉, 郎美东. 聚合物前药载药性能的计算机模拟[J]. 华东理工大学学报(自然科学版), 2020, 46(5): 631-641. doi: 10.14135/j.cnki.1006-3080.20190514001
引用本文: 罗雪莉, 郎美东. 聚合物前药载药性能的计算机模拟[J]. 华东理工大学学报(自然科学版), 2020, 46(5): 631-641. doi: 10.14135/j.cnki.1006-3080.20190514001
LUO Xueli, LANG Meidong. Computer Simulation on Drug Loading Efficiency of Polymeric Prodrug[J]. Journal of East China University of Science and Technology, 2020, 46(5): 631-641. doi: 10.14135/j.cnki.1006-3080.20190514001
Citation: LUO Xueli, LANG Meidong. Computer Simulation on Drug Loading Efficiency of Polymeric Prodrug[J]. Journal of East China University of Science and Technology, 2020, 46(5): 631-641. doi: 10.14135/j.cnki.1006-3080.20190514001

聚合物前药载药性能的计算机模拟

doi: 10.14135/j.cnki.1006-3080.20190514001
基金项目: 国家重点研发计划(2016YFC1100703);医用级聚碳酸酯的合成及在手术缝合线方面的应用开发。
详细信息
    作者简介:

    罗雪莉(1994-),女,浙江丽水人,硕士生,主要研究方向为药物载体。E-mail:lxl8129@163.com

    通讯作者:

    郎美东,E-mail:mdlang@ecust.edu.cn

  • 中图分类号: O631.1

Computer Simulation on Drug Loading Efficiency of Polymeric Prodrug

  • 摘要: 采用分子动力学模拟计算了药物接枝率不同时聚合物前药载体聚乙二醇单甲醚-b-聚(ε-己内酯-co-哌啶内酯-g-5-氨基酮戊酸)(mPEG- b -P(CL- co-APIL)中的疏水链段与药物5-氨基酮戊酸(5-ALA)之间的相容性,预测载体载药效率与药物接枝率之间的关系。采用耗散粒子动力学(DPD)模拟探索和观察载药胶束的形态和药物分子的聚集状态。计算结果表明,随着药物接枝率的增加,载体与药物之间的相容性变好;增加聚合物疏水段药物接枝率可以提高载体的载药效率。

     

  • 图  1  聚合物的分子结构

    Figure  1.  Molecular structure of polymers

    图  2  部分无定形模型的示意图

    Figure  2.  Schematic diagrams of partial amorphous models

    a—PCL20;b—PAPIL20;c—P(APIL10-co-CL10)/5-ALA;d—P(APIL10-co-CL10)/H2O

    图  3  mPEG-b-P(CL-co-APIL)(a),5-ALA(b)和H2O(c)的粗粒化模型

    Figure  3.  Coarse-grained models of mPEG-b-P(CL-co-APIL)(a), 5-ALA(b) and H2O(c)

    图  4  PAPIL20分子动力学模拟过程平衡图

    Figure  4.  Molecular dynamics simulation balance diagrams of PAPIL20

    图  5  分子结构式转化为分子模型的示意图

    Figure  5.  Schematic diagrams of the transformation of molecular structure into molecular models

    图  6  药物m-ALA接枝率不同时P(CL-co-APIL)的密度(a)及内聚能密度(b)

    Figure  6.  Density (a) and cohesion energy density (b) of P(CL-co-APIL) with different grafting ratios of m-ALA

    图  7  药物接枝率不同时P(CL-co-APIL)聚合物前药与5-ALA的Flory-Huggins相互作用参数

    Figure  7.  Flory-Huddins interaction parameters of P(CL-co-APIL) and 5-ALA calculated by MD with different drug grafting ratios

    图  8  不同模拟步数下mPEG-b-PCL20/5-ALA的DPD模拟自组装过程(红色为5-ALA,绿色为PCL,橙色为mPEG;Y(5-ALA)=0)

    Figure  8.  DPD simulation self-assembly of mPEG-b-PCL20/5-ALA at different simulation steps(Red: 5-ALA, Green: PCL, Orange: mPEG; Y(5-ALA)=0)

    图  9  不同模拟步数下mPEG-b-P(CL12-co-APIL8)/5-ALA的DPD模拟自组装过程(红色为5-ALA,绿色为PCL,蓝色为PAPIL,橙色为mPEG; Y(5-ALA)=40%)

    Figure  9.  DPD simulation self-assembly of mPEG-b-P(CL12-co-APIL8)/5-ALA at different simulation steps(Red: 5-ALA, Green: PCL, Blue: PAPIL, Orange: mPEG; Y(5-ALA)=40%)

    图  10  不同模拟步数下mPEG-b-PAPIL20/5-ALA的DPD模拟自组装过程(红色为5-ALA,蓝色为PAPIL,橙色为mPEG;Y (5-ALA)=100%)

    Figure  10.  DPD simulation self-assembly of mPEG-b-PAPIL20/5-ALA at different simulation steps(Red: 5-ALA, Green: PCL, Orange: mPEG;Y(5-ALA)=100%)

    图  11  5-ALA接枝率不同时聚合物前药的DPD模拟的形态图及剖面图(红色为5-ALA,绿色为PCL,橙色为mPEG)

    Figure  11.  DPD simulation morphology and section view of drug-loaded micelle with different 5-ALA grafting ratios (Red: 5-ALA, Green: PCL, Orange: mPEG)

    图  12  5-ALA接枝率不同时聚合物前药中5-ALA的密度分布

    Figure  12.  Density distribution of 5-ALA in polymeric prodrug with different 5-ALA grafting ratios

    图  13  5-ALA接枝率不同时的归一化密度分布曲线

    Figure  13.  Normalized density distribution of 5-ALA with different grafting ratios

    表  1  纯无定形体系中分子的物质的量和混合无定形体系中各分子的物质的量之比

    Table  1.   Molecular molar numbers of the compounds in pure amorphous system and molar ratio of the different compounds in mixed amorphous systems

    Pure amorphous systemn/molMixed amorphous systemMolecular molar ratios
    PCL208PCL20/5-ALA4/65
    P(CL18-co-APIL2)7P(CL18-co-APIL2)/5-ALA4/70
    P(CL16-co-APIL4)6P(CL16-co-APIL4)/5-ALA3/60
    P(CL14-co-APIL6)5P(CL14-co-APIL6)/5-ALA370
    P(CL12-co-APIL8)5P(CL12-co-APIL8)/5-ALA3/70
    P(APIL10-co-CL10)5P(CL10-co-APIL10)/5-ALA3/70
    P(CL8-co-APIL12)4P(CL8-co-APIL12)/5-ALA2/65
    P(CL6-co-APIL14)4P(CL6-co-APIL14)/5-ALA2/70
    P(CL4-co-APIL16)4P(CL4-co-APIL16)/5-ALA2/70
    P(CL2-co-APIL18)3P(CL2-co-APIL18)/5-ALA2/70
    PAPIL203PAPIL20/5-ALA2/70
    m-ALA1205-ALA/H2O20/1 000
    5-ALA150m-ALA/H2O15/1 000
    H2O1 000mPEG/H2O2/900
    mPEG20mPEG/m-ALA20/15
    mPEG/PAPIL15/2
    mPEG/PCL10/4
    mPEG/5-ALA20/16
    下载: 导出CSV

    表  2  纯无定形体系的密度和内聚能密度

    Table  2.   Density and cohesive energy density of pure amorphous system

    Systemρ/(g·cm−3)ρcoh/(108 J·m−3)ρcoh-vdw/(108 J·m−3)ρcoh-e/(108 J·m−3)
    PCL201.064 93.276 73.038 00.238 7
    PPIL201.137 03.701 43.140 60.560 8
    PAPIL201.216 74.153 33.007 81.145 5
    PCCL201.156 54.018 43.226 00.792 4
    PmACCL201.180 53.432 02.660 90.771 1
    5-ALA1.212 610.119 94.066 46.053 5
    m-ALA1.105 45.893 84.258 51.635 3
    下载: 导出CSV

    表  3  分子之间的Flory-Huggins相互作用参数

    Table  3.   Flory-Huggins interactional parameters of molecules

    Systemχijχij-vdwχij-e
    PCL20/5-ALA 1.13 0.34 0.79
    PmACCL20/5-ALA 1.35 0.14 1.21
    PCCL20/5-ALA −0.54 −0.49 −0.05
    PAPIL20/5-ALA −2.65 −2.59 −0.06
    PPIL20/5-ALA −0.84 −0.70 −0.14
    PCL20/m-ALA 0.16 −0.16 0.32
    PmACCL20/m-ALA −2.49 −1.75 −0.74
    PCCL20/m-ALA −2.45 −0.51 −1.94
    PAPIL20/m-ALA −1.47 −1.15 −0.32
    PPIL20/m-ALA −0.32 −0.27 −0.05
    PCL20/H2O 8.85 −1.94 10.79
    PmACCL20/H2O 4.92 −1.03 5.95
    PCCL20/H2O 1.44 3.11 −1.67
    PAPIL20/H2O 5.70 −1.15 6.85
    PPIL20/H2O 4.33 −1.03 5.36
    5-ALA/mPEG 0.30 0.24 0.06
    5-ALA/H2O 0.66 0.05 0.61
    m-ALA/mPEG 0.42 0.32 0.10
    m-ALA/H2O 1.41 −0.19 1.60
    mPEG/PmACCL −0.31 −0.19 −0.12
    mPEG/PCL 0.81 0.61 0.20
    mPEG/H2O 0.36 0.00 0.36
    PmACCL/PCL −0.53 −0.81 0.28
    下载: 导出CSV

    表  4  各珠子之间的Flory-Huggins相互作用参数

    Table  4.   Flory-Huggins interaction parameters between beads

    Bead χij
    EPCWA
    E 0
    P −0.48 0
    C 0.81 1.62 0
    W 0.38 5.37 8.85 0
    A 0.30 −2.56 1.26 0.66 0
    下载: 导出CSV

    表  5  各珠子之间的排斥参数

    Table  5.   Repulsive parameters between beads

    BeadRepulsive parameters
    EPCWA
    E 25.00
    P 23.33 25.00
    C 27.82 30.68 25.00
    W 26.33 43.77 55.94 25.00
    A 26.06 16.06 29.41 27.30 25.00
    下载: 导出CSV
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出版历程
  • 收稿日期:  2019-05-14
  • 网络出版日期:  2019-10-22
  • 刊出日期:  2020-10-30

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