Convection-Enhanced Drug Delivery: Experimental and Analytical Studies of Infusion Behavior in an In Vitro Brain Surrogate

Ann Biomed Eng. 2024 Mar 19. doi: 10.1007/s10439-024-03482-4. Online ahead of print.ABSTRACTConvection-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 infus...
Source: Annals of Biomedical Engineering - Category: Biomedical Engineering Authors: Source Type: research