聚合物前药载药性能的计算机模拟

Computer Simulation on Drug Loading Efficiency of Polymeric Prodrug

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.