Mesh : Hydrogels / chemistry Brain / metabolism Animals Drug Delivery Systems / instrumentation methods Convection Fluorescent Dyes / chemistry administration & dosage Male Rats

来  源:   DOI:10.1038/s42003-024-06404-1   PDF(Pubmed)

Abstract:
Electrokinetic convection-enhanced delivery (ECED) utilizes an external electric field to drive the delivery of molecules and bioactive substances to local regions of the brain through electroosmosis and electrophoresis, without the need for an applied pressure. We characterize the implementation of ECED to direct a neutrally charged fluorophore (3 kDa) from a doped biocompatible acrylic acid/acrylamide hydrogel placed on the cortical surface. We compare fluorophore infusion profiles using ECED (time = 30 min, current = 50 µA) and diffusion-only control trials, for ex vivo (N = 18) and in vivo (N = 12) experiments. The linear intensity profile of infusion to the brain is significantly higher in ECED compared to control trials, both for in vivo and ex vivo. The linear distance of infusion, area of infusion, and the displacement of peak fluorescence intensity along the direction of infusion in ECED trials compared to control trials are significantly larger for in vivo trials, but not for ex vivo trials. These results demonstrate the effectiveness of ECED to direct a solute from a surface hydrogel towards inside the brain parenchyma based predominantly on the electroosmotic vector.
摘要:
电动对流增强递送(ECED)利用外部电场通过电渗和电泳将分子和生物活性物质递送到大脑的局部区域,不需要施加的压力。我们表征了ECED的实施方式,以从放置在皮质表面的掺杂的生物相容性丙烯酸/丙烯酰胺水凝胶中引导中性电荷的荧光团(3kDa)。我们使用ECED(时间=30分钟,电流=50µA)和仅扩散对照试验,用于离体(N=18)和体内(N=12)实验。与对照试验相比,ECED中注入大脑的线性强度曲线明显更高,体内和离体。输液的直线距离,输液面积,与对照试验相比,ECED试验中的峰值荧光强度沿输注方向的位移在体内试验中明显更大,但不用于体外试验。这些结果证明了ECED主要基于电渗载体将溶质从表面水凝胶引向脑实质内部的有效性。
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