In Silico Investigation of Electrically Guided Drug Transport Toward Morphology-Specific Brain Tumor Treatment

Background/Objectives: Iontophoresis employs an applied electric field to induce electromigration, enabling the active and directional transport of drug molecules. This study presents the first computational investigation of iontophoretic drug delivery targeting human brain tumors. The objective was to evaluate the feasibility of this approach and to determine how electrode configurations influence drug transport across different tumor morphologies. Methods: A realistic finite element head model was constructed from T1-weighted magnetic resonance imaging data. Two representative glioblastoma morphologies were considered: a spherical tumor in the left hemisphere and a butterfly-shaped tumor extending across the corpus callosum. Six electrode configurations spanning three categories (scalp electrodes, combined catheter and scalp electrodes, and catheter electrodes) were systematically evaluated. The electric field distribution was computed by solving the quasi-static Laplace equation, and the spatiotemporal distribution of gadobutrol was obtained using the Nernst–Planck equation. Drug delivery performance was quantified in terms of tumor coverage and targeting efficiency. Results: Under the simulated conditions, iontophoresis markedly enhanced drug delivery compared with passive diffusion, increasing tumor volume coverage from 13% to 84% in the spherical tumor model. Scalp electrode configurations resulted in the lowest tumor coverage in both tumor models. The combined catheter–scalp configuration generated radial drug transport from the catheter and achieved the highest coverage in the spherical tumor. In the butterfly-shaped tumor model, a three-catheter configuration enabled bilateral delivery along the tumor axis, achieving a tumor coverage of 49% and a targeting efficiency of 82%. The maximum electric field magnitude across all configurations was 49.26 V/m, remaining below reported axonal activation thresholds for deep brain stimulation. Conclusions: These findings support the feasibility of iontophoretic drug delivery to human brain tumors and demonstrate that the effective electrode configuration depends on tumor morphology. This study provides a computational foundation for morphology-specific planning of iontophoretic drug delivery to brain tumors.