Experimental Study Of Drug-carrying Antimicrobial Hydrogel Force Response DPD/MD Simulation

The amphiphilic block copolymer is biocompatible and degradable,and the stimulating block it contains can self-assemble in aqueous solution to form shell-nucleus structure micelles,which provides a natural transport channel for drugs.On the other hand,the presence of both hydrophobic and hydrophilic blocks in the same copolymer system forms micelles with dense and hydrophobic cores,which are suitable for loading hydrophobic drugs,and loose and hydrophilic shells,which can effectively avoid aggregation and precipitation between micelles,playing an important role in improving micelle solubility,environmental stability and drug timeliness.In the field of drug release,block copolymer self-assembled micelles will easily deform and rupture under mechanical loading conditions,which can achieve a long time effective controlled drug release.These advantages of block copolymer micelles have become a very attractive drug carrier material in the field of regenerative medicine.Although a large number of experimental studies have been conducted,a deeper understanding of the kinetic mechanism of micelle self-assembly and the kinetic triggers of drug loss needs to be investigated at the molecular level.In this thesis,we selected F127(PEO₉₉-PPO₆₅-PEO₉₉)as a candidate matrix and rifampicin（Rif）as an antibacterial drug for a representative F127-Rif hydrogel system,and used a combination of molecular dynamics（MD）and dissipative particle dynamics（DPD）to realize the whole process of self-assembly and mechanically responsive drug release of the block copolymer.In order to present the molecular assembly behavior,kinetic mechanism and thermodynamic triggers at the molecular level,and to provide theoretical guidance for the preparation of more efficient encapsulation and transport of hydrophilic drug carrier hydrogels.A combination of DPD simulation and molecular dynamics simulation techniques was used to visualize the reproduction of the self-assembly process of F127-Rif drug-loaded micelles and to investigate the molecular dynamics mechanism of the self-assembly process.F127(PEO₉₉-PPO₆₅-PEO₉₉)was selected as the amphiphilic block copolymer substrate and rifampicin（Rif）as the antimicrobial drug,and the mesoscale simulation of the self-assembly process of PEO₉₉-PPO₆₅-PEO₉₉and Rif forming F127-Rif drug-loaded micelles in aqueous environment was realized.The effect of drug loading on the self-assembly morphology of F127-Rif drug-loaded micelles was investigated,and the optimal drug loading of F127-Rif drug-loaded micelles at 30%mass fraction of F127 was further investigated.The simulation results showed that the molecular mechanism of self-assembly of F127-Rif hydrogels is that F127 can load the strongly hydrophobic antibiotic rifampicin in the core of the micelles by its hydrophobic association;the whole assembly process is not dependent on the content of each substance,but can form a core-shell micelle with PPO as the core,PEO as the shell and Rif drug molecules in the center.Simulation of the self-assembly process of F127-Rif drug-loaded micelles at a mass fraction of 30%revealed that when the drug loading was low,F127-Rif drug-loaded micelles could be assembled to form several relatively dispersed small micelles,and as the drug loading increased to about 10%-13%,the micelles gradually became larger to form a relatively complete micelle,and further increased to 15%-20%,the drug became more fragile due to exceeding the polymer The drug is easily exposed and loses its coating effect as the coating limit of the polymer gel is exceeded.Molecular dynamics simulations were performed to investigate the drug release mechanism of F127-Rif drug-loaded micelles loaded with Rif drugs under tensile loading.The simulation results showed that the deformation of the drug-loaded micelles caused by the increase of tensile load would lead to the increase of the intermolecular lattice size of the shell-core of the micelles,which would promote the release of the encapsulated drug and achieve the purpose of controlled drug release.Under tensile loading,the hydrophobic binding of the micelles is disrupted and the drug molecules are gradually released due to the loss of micelle binding.As the tensile load increases,the Rif drug molecules become more active and are gradually released from the micelles.At an external load of 90 kcal/mol/?,the micelles were severely stretched and deformed,and the drug molecules diffused most vigorously.For the controlled drug release performance of F127-Rif drug-loaded micelles self-assembled under compression loading,molecular dynamics simulations were used to study the drug release mechanism of F127-Rif drug-loaded micelles loaded with different compression loads,and the simulation results showed that the release increased slightly with increasing compression load,and the difference was not large,and the difference was more obvious only at the later stage of the simulation,from the perspective of drug delivery From a drug delivery perspective,the small release per cycle observed here is very interesting as it would allow the system to work longer before drug depletion.At higher compressive loads,the micelles are again severely compressed and deformed,and the F127-Rif micelles split completely at the end of the simulation,leading to carrier failure.In conclusion,a compression load value of90-110 kcal/mol/?is more appropriate for the designed hydrogel product.