Study On Self-assembly Behavior Of Drug Delivery System Based On Dissipative Particle Dynamics

Drug delivery system,an engineering technology based on personalized design of drug delivery systems,aims to improve efficacy and reduce side effects.Several novel materials such as nanoparticles and hydrogels have been used in the design of different drug delivery systems.However,the huge time cost and economic burden limit the experimental development of novel and efficient drug delivery methods.Moreover,it is a challenge to study their controlled release mechanisms at the molecular level by conventional experimental methods.Dissipative particle dynamics(DPD)is a mesoscopicscale simulation tool that is widely used in materials research due to its unique advantages at the time and space scales.In this paper,we will use DPD to investigate the self-assembled structures and stability differences of two materials commonly used in drug delivery systems,nanoparticles and hydrogels.The main work of this thesis is as follows:(1)The conventional oral atorvastatin calcium is less efficient and can cause drug wastage,so to improve efficiency and reduce toxic side effects,amphiphilic nanoparticles can be used for drug delivery to compensate for the shortcomings of the conventional approach.Due to the limitation of traditional experimental methods,finding the most suitable molecular conformation of amphiphilic polymers requires a lot of financial and material resources.Therefore,in this study,the structural stability and drug loading capacity of amphiphilic nanoparticles formed by self-assembly of diblock and triblock polymers with different hydrophilic ratios were investigated by using DPD.By comparing the binding strength of poly(lactic acid)(PLA)and poly(ethylene glycol)(PEG)in nanoparticles,the morphological changes of nanoparticles in the shear fluid field and the hydrophilic surface coverage of nanoparticles,the length of polymer hydrophobic chains was found to be a key factor affecting the stability of nanoparticles.The effect of the difference of drug loading on the stability of nanoparticles was also investigated.(2)Based on the discussion of the stability of nanoparticles in the previous chapter,this part will deepen the study of the stability of nanoparticles under the shear field of blood circulation.Amphiphilic molecules with different topologies were constructed in this study,and by comparing the morphological changes of their self-assembled nanoparticles formed in the shear fluid field,it was found that the degree of molecular branching and geometric symmetry are the key factors to maintain the stability of nanoparticles.And by comparing the changes of energy in the system,it is found that the system energy will produce large fluctuations when the nanoparticles are broken.(3)The characterization of network structure of hydrogels has always been a difficult problem in the field of molecular simulation.Based on the previous work,we used multi-scale simulation to explore the microstructure evolution of glycyrrhizic acid hydrogels induced by p H.Glycyrrhizic acid is a natural small molecule that can self-assemble to form hydrogels under specific conditions.The concentration of the polymer as well as the p H value of the environment play an important role in the self-assembly process.In this study,we used allatom simulations to analyze and explain the aggregation behavior of glycyrrhizic acid in different acid-base environments and DPD to provide a mesoscopic-level understanding of the mechanism of p H-induced glycyrrhizic acid self-assembly.The results show that glycyrrhizic acid tends to selfaggregate and form ordered structures such as spheres,columns and membranes in acidic environment.Disordered polydisperse microspheres or worm-like structures tend to be formed in alkaline environments.The three-dimensional gel network structure can be formed only in neutral or near-neutral environment and appropriate concentration.In the end,we summarize the contents of this work,put forward the shortcomings,and look forward to the future.