Interfacial Regulation Of PH/light-responsive Amphiphilic Alginate And The Mechanism Of Stabilization/destabilization Of Drug-loaded Pickering Emulsion

The development of a green-friendly intelligent drug delivery system with maximum drug utilization is a hot spot in the current era of great health and the grand strategy of protecting the environment.However,the evolution of interface multi-scale structure in intelligent drug-loading system and the interface micro-mechanism of the interaction between surfactants and nanoparticles are still common basic research issues in related application development.Therefore,the aim of this study is to take the coumarin-based alginate pH/UV responsive intelligent drug-loaded emulsion as the research object,and use the scientific research method combination of computer simulation and experimental analysis to explore the structural evolution of the interfacial aggregates,synergistic stabilization mechanism and controlled-release/extended-release mechanism,so as to provide the applied theoretical basis for the design and preparation of an intelligent drug-loaded emulsion with high drug utilization rate.The main contents and key points are as follows:（1）The amphiphilic sodium alginate derivative（SA-AMC）was synthesized by modifying sodium alginate（SA）with coumarin（AMC）using Ugi reaction.The structure of SA-AMC was characterized by FT-IR,UV-Vis and¹H NMR spectroscopy.The effects of pH and UV on the stability of emulsion formed by SA-AMC were studied by Coarse-Grained Molecular Dynamics（CGMD）and experiment.The simulation showed that the emulsion self-assembly process could be divided into approaching,adsorption and migration.At pH=4.15,SA-AMC shrunk due to low electrostatic repulsion,resulting in droplet reduction and stability improvement;after 365 nm UV irradiation,the structure was more compact due to the dimerization of AMC,which was conducive to further stability of the emulsion.The effects of pH and UV on the stability of emulsion formed by SA-AMC were elucidated on the multiscale,and visualized the emulsification/demulsification process.（2）The drug-loading/release process and properties of the emulsion formed by SA-AMC were further explored.The simulation process showed that the curcumin（CUR）originally accumulated inside the oil drop would migrate continuously and disperse on the surface of the oil droplet.Through the exploration of the composition of the system,the optimal composition of the drug-loading system was finally determined to be PAR₈₀-CUR₂₅-AMC₄₀.In addition,the drug-loading efficiency of emulsion formed by SA-AMC-Al decreased from 72%to 64%in alkaline condition,and the aggregation of CUR decreased the drug-loading stability.Under photodimerization,the drug-loading efficiency of emulsion formed by SA-AMC-Di increased to 76%,achieving the better extended-release effect.The responsiveness of SA-AMC drug-loaded emulsion in alkaline environment is expected to enhance the targeted release efficiency of cancer drugs and achieve controlled release.（3）SiO₂was used to synergistically stabilize the emulsion.The effects of SiO₂concentrations,pH and UV on the stability,the drug-loading and releasing ability of the emulsion formed by SA-AMC/SiO₂were studied by combining CGMD with experiments.The results showed that with the increase of SiO₂concentrations,SiO₂could combine with SA-AMC to form SA-AMC/SiO₂composite micelles,and the stability of emulsion could be improved by synergistic effect.In addition,the simulation and experiment results showed that the stability of emulsion formed by SA-AMC/SiO₂increased under acidic condition and 365 nm UV.In terms of drug-loading and release behavior,the drug-loading efficiency of SA-AMC/SiO₂stabilized emulsion decreased from 84%to 80%in alkaline condition;while under photodimerization,the drug-loading efficiency of SA-AMC-Di/SiO₂stabilized emulsion increased to 96%,achieving the better extended-release effect.The SA-AMC/SiO₂drug-loaded emulsion system also showed controlled drug-release ability in alkaline environment,which made up for the deficiency of emulsions in the field of simulation.In general,this paper is based on seaweed resources and the needs of health and environmental protection.The research method of combining theory with experiment can improve efficiency,reduce cost,and provide a certain theoretical basis for the application of other intelligent drug delivery systems in potential fields.