Brain drug delivery is governed by coupled fluid transport, tissue deformation and particle diffusion across multiple scales. We developed a bottom-up modelling framework that resolves fluid–axon and particle–tissue interactions and upscales them into anisotropic, pressure- and deformation-dependent tissue transport properties [1–7]. These properties were incorporated into whole-brain models of convection-enhanced drug delivery, which predict how tissue microstructure and catheter orientation influence drug distribution [8].
The framework was validated across scales using imaging and biomechanical measurements, and its organ-scale predictions were evaluated against longitudinal MRI measurements of tracer transport in living sheep brains [9]. An in vivo study directly quantified how diffusion-tensor-imaging-derived white matter architecture and catheter positioning constrain infusate distribution [10].
A coupled blood–vessel–brain model further demonstrates that pulsatile blood flow continuously deforms the brain tissues, with deformation increasing under elevated blood pressure [11]. Because tissue permeability changes with microstructural deformation, these results suggest that vascular pulsatility may dynamically modulate interstitial transport and infused drug distribution. Together, the models connect multiscale and multiphysics mechanics, in vivo validation and haemodynamics, providing a basis for patient-specific planning of precision brain drug delivery.

References
1. Yuan T, Gao L, Zhan W, Dini D. Pharm Res. 2022;39:767–781.
2. Yuan T, Yang Y, Zhan W, Dini D. Int J Mol Sci. 2023;24:2534.
3. Yuan T, Zhan W, Jamal A, Dini D. Biomech Model Mechanobiol. 2022;21:1299–1316.
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8. Yang Y, Yuan T, Rodriguez y Baena F, et al. J R Soc Interface. 2024;21:20240378.
9. Yuan T, et al. bioRxiv [Preprint]. 2025. doi:10.1101/2025.03.22.643151.
10. Castellano A, et al. bioRxiv [Preprint]. 2025. doi:10.1101/2025.04.15.648763.
11. Gao X, et al. Int J Mech Sci. 2025;296:110278.


Contatti:
paola.antonietti@polimi.it