Molecular Simulation Methods To Optimize Structure And Properties Of Lipid Nanoparticle Delivery System

Nanostructured lipid carriers (NLC) composed of a solid lipid matrix with a certain content of liquid lipid are a new generation of lipid nanoparticle delivery system. The special structure of NLC improves its drug-loading capacity and stability, and effectively controls the release of drugs. NLC are complex multi-phase systems, whose composition and preparation parameters impose effect on their properties by means of changing their nanostructure. In this study, molecular simulation, theoretical analysis and experimental characterization are integratively used to expound the forming mechanism of lipid nanoparticles from molecular dynamics and mesoscopic dynamics, the effects on their nanostructures imposed by their composition and preparation parameters are studied, the changes of NLC structure and properties are grasped, the quantitative relationship of macroeconomic conditions, nanostructures and pharmaceutical performance are established.In NLC drug delivery systems, the compatibility of drug and lipid carriers is the key element to determine the structure of microscopic and mesoscopic, drug-loading capacity and stability. In this study, molecular dynamics simulation method combining Flory-Huggins theory is used to calculate solubility parameter of drug and carriers, predict the blends performance of drug and different carriers, and then screen out the ideal ratio of the amount of lipid carriers.The nanostructures and properties of NLC are further investigated with Dissipative Particle Dynamics (DPD) simulation technique. DPD simulation technique can show the processes and phenomena which are difficult to be displayed by experiments, and can effectively analyze mesoscopic structure and forming mechanism of lipid nanoparticle drug delivery system. Their composition and preparation parameters are screened and optimized by mesoscopic simulation and theoretical analysis. DPD simulation technique cannot only ensure qualitatively analysis of the experimental phenomena, but also quantitatively forecast of experimental results.In the basis of the molecular modeling experiments, D-optimal mixture experimental design is used to optimize synchronously NLC drug delivery system by multiple indicator, which has fewer test points, reliable results, and high-precision forecast. Based on the evaluation of optimal NLC, the experimental results better match the theoretical prediction of molecular simulation, which further proves the accuracy and reliability of molecular simulation forecasts.In this study, molecular simulation technology is used for theoretical research and designing optimization of lipid nanoparticle system, which can reduce repeated experiments, shorten the research cycle, save a lot of research costs, speed up the pharmaceutical process of research and development. Molecular simulation techniques used in the pharmaceutical field have a strong practical value, which contribute to the development of new pharmaceutical techniques and theories.