Computer Simulation on Drug Loading Efficiency of Polymeric Prodrug

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.