对流增强的药物递送(CED)直接向靶细胞注入具有大分子量的药物,作为神经退行性疾病和脑癌的治疗策略。尽管先前许多关于CED的体外实验都取得了成功,挑战依然存在。特别是,需要一个理论预测模型来形成治疗计划的基础,开发这样的模型需要良好控制的注射测试,可以严格捕获注入液的对流(对流)和扩散传输。为此,我们研究了在不同的注射速率下,在大脑替代(0.2%w/w琼脂糖凝胶)中注入液(溴酚蓝溶液)的平流-扩散传输,范围从0.25到4μL/min,通过密切监测颜色强度的变化,传播距离,和注射压力。用两个变量集检查一维封闭形式的解,如数学计算的分子扩散系数和平均速度,用最小二乘方法计算水力分散系数和渗流速度。因此,渗流速度在一定程度上大于平均速度,特别是对于以后的输液时间。替代大脑中的多孔弹性变形可能导致孔隙率的变化,因此,随着输注的继续,实际流速略有增加。通过无量纲分析分析了单导管的效率限制。最后,这项研究提出了一种简单但可靠的方法,可以通过控制良好的注射测试正确捕获体外脑替代物中输注液的对流(对流)和扩散运输。
Convection-enhanced drug delivery (CED) directly infuses drugs with a large molecular weight toward target cells as a therapeutic strategy for neurodegenerative diseases and brain cancers. Despite the success of many previous in vitro experiments on CED, challenges still remain. In particular, a theoretical predictive model is needed to form a basis for treatment planning, and developing such a model requires well-controlled injection tests that can rigorously capture the convective (advective) and diffusive transport of an infusate. For this purpose, we investigated the advection-diffusion transport of an infusate (bromophenol blue solution) in the brain surrogate (0.2% w/w agarose gel) at different injection rates, ranging from 0.25 to 4 μL/min, by closely monitoring changes in the color intensity, propagation distance, and injection pressures. One dimensional closed-form solution was examined with two variable sets, such as the mathematically calculated coefficient of molecular diffusion and average velocity, and the hydraulic dispersion coefficient and seepage velocity by the least squared method. As a result, the seepage velocity was greater than the average velocity to some extent, particularly for the later infusion times. The poroelastic deformation in the brain surrogate might lead to changes in porosity, and consequently, slight increases in the actual flow velocity as infusion continues. The limitation of efficiency of the single catheter was analyzed by dimensionless analysis. Lastly, this study suggests a simple but robust approach that can properly capture the convective (advective) and diffusive transport of an infusate in an in vitro brain surrogate via well-controlled injection tests.