Multi-scale Simulation Method For Drug Delivery System

Since the 21st century,the concept of nanomedicine adjuvant therapy has been widely accepted.The design of transdermal drug delivery microneedle(MN)drug delivery system containing drug-loaded nanoparticles has been proved as an excellent match.However,due to the multiple components and complex microstructures of such systems,theoretical research is still incomplete.In order to overcome these difficulties,the researchers have developed a dissipative particle dynamics(DPD)simulation method based on the mesoscopic space-time scale.Insight from the practice of polymer MN production,this article will discuss the application of DPD simulation for MN from three aspects.The main work of the thesis is as follows:(1)The differences in the control of drug distribution between hyaluronic acid(HA)and polyvinyl alcohol(PVA)MNs have investigated through multiscale simulation methods,the results of which show that the diffusion coefficient of SRB in PVA solution is lower than that in HA solution,which can effectively prevent the diffusion of drugs from the tip of the microneedle to the base.Finally,PVA and HA MNs loaded with SRB were prepared,and the simulation results were compared with the experimental results.,Finally,we have also analyzed the different diffusion mechanisms of insulin in the MNs in similar manners.(2)A new mechanism for the self-assembly of amphiphilic polymers through the dynamic modelling of the dialysis process has been purposed.We found that the polymer undergoes four phase transition states during the dialysis process:(ⅰ)Dispersed state.(ⅱ)Pre micelle state.(ⅲ)Over micellar state.(iv)Final state.The simulation results prove that the interaction strength between the organic solvent and the hydrophobic segment of the polymer is very critical,which also has a negative impact on the drug-carrying performance of the microspheres.(3)A series of DPD simulations have been exerted to demonstrate how the pH conditions play a key role in rhein hydrogel processing.The research results show that in an acidic environment,rhein molecules tend to aggregate,only forming precipitation.In the alkaline environment,rhein molecules form a series of discontinuous and highly dispersible structures with good thermodynamic stability but without required mechanical properties,staying in the state of solution.As the pH is moderate,rhein molecules can form a continuous network structure,which has both thermodynamic stability and good mechanical properties.