文献类型：期刊文献

中文题名：聚合物前药载药性能的计算机模拟

英文题名：Computer Simulation on Drug Loading Efficiency of Polymeric Prodrug

作者：罗雪莉[1];郎美东[1]

机构：[1]上海市先进聚合物材料重点实验室,华东理工大学材料科学与工程学院,上海200237

年份：2020

卷号：46

期号：5

起止页码：631

中文期刊名：华东理工大学学报（自然科学版）

外文期刊名：Journal of East China University of Science and Technology

收录：CSTPCD;;Scopus;北大核心:【北大核心2017】；CSCD:【CSCD_E2019_2020】；

基金：国家重点研发计划(2016YFC1100703)。

语种：中文

中文关键词：计算机模拟;前药;药物载体;嵌段共聚物

外文关键词：computer simulation;prodrug;drug carrier;block copolymer

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。
To explore the relationship between drug grafting ratio of polymeric prodrugs and their drug-loading efficiency,a model polymeric prodrug,methoxy poly(ethylene glycol)-b-poly(ε-caprolactone-co-piperilactone-g-5-aminolevulinic acid)(mPEG-b-P(CL-co-APIL)),was prepared.This prodrug was used as a drug carrier of 5-aminolevulinic acid(5-ALA)through both covalent bonding and non-covalent embedding.Molecular dynamics(MD)was used to calculate the compatibility of the polymeric prodrug with 5-ALA and H2O molecules,and to predict the relationship between the drug grafting ratio and drug loading.On calculation,the Flory-Huggins interactional parameter was decomposed into van der Waals force components and electrostatic force components for analyzing the effect of 5-ALA grafting ratio on the polymeric prodrug carrier.Dissipative particle dynamics simulation(DPD)was used to explore and observe the morphology of the drug-loaded micelles and the concentration state of the drug molecules.Computational simulation results showed that the compatibility between polymeric prodrug and 5-ALA improved with an increasing drug grafting ratio,leading to a prediction that the drug loading efficiency of polymeric drug would improve as the drug grafting ratio increased.Meanwhile,the DPD simulation showed that the polymeric prodrug self-assembled into spherical micelles in H2O.The density distribution of drug molecules suggested that the drug concentration in the core of the micelle was high because of a higher drug grafting ratio.All the simulation results suggested the feasibility of improving drug loading efficiency by increasing drug-molecule grafting ratios.This research offers guidance for the design and development of drug carriers.