PDF(Pubmed)
Abstract：
BACKGROUND: The rapid growth and diversification of drug delivery systems have been significantly supported by advancements in micro- and nano-technologies, alongside the adoption of biodegradable polymeric materials like poly(lactic-co-glycolic acid) (PLGA) as microcarriers. These developments aim to reduce toxicity and enhance target specificity in drug delivery. The use of in silico methods, particularly molecular dynamics (MD) simulations, has emerged as a pivotal tool for predicting the dynamics of species within these systems. This approach aids in investigating drug delivery mechanisms, thereby reducing the costs associated with design and prototyping. In this study, we focus on elucidating the diffusion mechanisms in curcumin-loaded PLGA particles, which are critical for optimizing drug release and efficacy in therapeutic applications.
METHODS: We utilized MD to explore the diffusion behavior of curcumin in PLGA drug delivery systems. The simulations, executed with GROMACS, modeled curcumin molecules in a representative volume element of PLGA chains and water, referencing molecular structures from the Protein Data Bank and employing the CHARMM force field. We generated PLGA chains of varying lengths using the Polymer Modeler tool and arranged them in a bulk-like environment with Packmol. The simulation protocol included steps for energy minimization, T and p equilibration, and calculation of the isotropic diffusion coefficient from the mean square displacement. The Taguchi method was applied to assess the effects of hydration level, PLGA chain length, and density on diffusion.
RESULTS: Our results provide insight into the influence of PLGA chain length, hydration level, and polymer density on the diffusion coefficient of curcumin, offering a mechanistic understanding for the design of efficient drug delivery systems. The sensitivity analysis obtained through the Taguchi method identified hydration level and PLGA density as the most significant input parameters affecting curcumin diffusion, while the effect of PLGA chain length was negligible within the simulated range. We provided a regression equation capable to accurately fit MD results. The regression equation suggests that increases in hydration level and PLGA density result in a decrease in the diffusion coefficient.
METHODS: We utilized MD to explore the diffusion behavior of curcumin in PLGA drug delivery systems. The simulations, executed with GROMACS, modeled curcumin molecules in a representative volume element of PLGA chains and water, referencing molecular structures from the Protein Data Bank and employing the CHARMM force field. We generated PLGA chains of varying lengths using the Polymer Modeler tool and arranged them in a bulk-like environment with Packmol. The simulation protocol included steps for energy minimization, T and p equilibration, and calculation of the isotropic diffusion coefficient from the mean square displacement. The Taguchi method was applied to assess the effects of hydration level, PLGA chain length, and density on diffusion.
RESULTS: Our results provide insight into the influence of PLGA chain length, hydration level, and polymer density on the diffusion coefficient of curcumin, offering a mechanistic understanding for the design of efficient drug delivery systems. The sensitivity analysis obtained through the Taguchi method identified hydration level and PLGA density as the most significant input parameters affecting curcumin diffusion, while the effect of PLGA chain length was negligible within the simulated range. We provided a regression equation capable to accurately fit MD results. The regression equation suggests that increases in hydration level and PLGA density result in a decrease in the diffusion coefficient.
摘要：
背景：药物递送系统的快速增长和多样化得到了微米和纳米技术进步的显着支持，同时采用可生物降解的聚合物材料，如聚（乳酸-共-乙醇酸）（PLGA）作为微载体。这些发展旨在降低毒性并增强药物递送中的靶特异性。使用计算机模拟方法，特别是分子动力学(MD)模拟，已经成为预测这些系统中物种动态的关键工具。这种方法有助于研究药物输送机制，从而降低了与设计和原型制作相关的成本。在这项研究中,我们专注于阐明姜黄素负载的PLGA颗粒中的扩散机制，这对于优化治疗应用中的药物释放和功效至关重要。
方法：我们利用MD探索姜黄素在PLGA药物递送系统中的扩散行为。模拟，用GROMACS执行，在PLGA链和水的代表性体积元素中模拟姜黄素分子，引用蛋白质数据库中的分子结构，并采用CHARMM力场。我们使用PolymerModeler工具生成了不同长度的PLGA链，并使用Packmol将它们排列在块状环境中。仿真协议包括能量最小化的步骤，T和p平衡，并根据均方位移计算各向同性扩散系数。Taguchi方法用于评估水化水平的影响，PLGA链长,和扩散密度。
结果：我们的结果提供了对PLGA链长的影响的见解，水合水平，和聚合物密度对姜黄素扩散系数的影响，为有效的药物输送系统的设计提供了机械的理解。通过Taguchi方法获得的敏感性分析确定水合水平和PLGA密度是影响姜黄素扩散的最重要的输入参数，而PLGA链长的影响在模拟范围内可以忽略不计。我们提供了一个能够准确拟合MD结果的回归方程。回归方程表明，水合水平和PLGA密度的增加导致扩散系数的降低。
方法：我们利用MD探索姜黄素在PLGA药物递送系统中的扩散行为。模拟，用GROMACS执行，在PLGA链和水的代表性体积元素中模拟姜黄素分子，引用蛋白质数据库中的分子结构，并采用CHARMM力场。我们使用PolymerModeler工具生成了不同长度的PLGA链，并使用Packmol将它们排列在块状环境中。仿真协议包括能量最小化的步骤，T和p平衡，并根据均方位移计算各向同性扩散系数。Taguchi方法用于评估水化水平的影响，PLGA链长,和扩散密度。
结果：我们的结果提供了对PLGA链长的影响的见解，水合水平，和聚合物密度对姜黄素扩散系数的影响，为有效的药物输送系统的设计提供了机械的理解。通过Taguchi方法获得的敏感性分析确定水合水平和PLGA密度是影响姜黄素扩散的最重要的输入参数，而PLGA链长的影响在模拟范围内可以忽略不计。我们提供了一个能够准确拟合MD结果的回归方程。回归方程表明，水合水平和PLGA密度的增加导致扩散系数的降低。
