Computational fluid-particle dynamic model guiding bioengineered magnetic nanomedicine for personalized brain-targeted drug delivery

Neurodegenerative diseases pose significant challenges to global healthcare, exacerbated by complexities of the central nervous system and blood–brain barrier. While FDA-approved magnetic nanocarriers offer promising solutions for targeted drug delivery, inherent challenges in predicting delivery performance still hinder clinical practice. Existing brain vasculature transport models often lack accuracy in the 3D construction of the brain vasculature network and physiology of blood circulation, limiting progress in targeted drug delivery. This paper introduced the Circle of Willis’s novel computational fluid dynamics framework to address these challenges. Utilizing patient-specific vascular geometries and incorporating complexities of blood circulation, hemodynamics, and the rheology for non-Newtonian fluid effect, our approach provides unprecedented insights into drug carrier dynamics in the mouse brain vasculature. Furthermore, we performed a comparative study simulating the dynamic transport using three types of magnetic nanocarriers—gold-coated superparamagnetic iron oxide (Au-SPIO), hollow-gold nano-shell enclosed superparamagnetic iron oxide (HGNS-SPIO), and metal–organic frameworks loaded with iron oxide (MOF-Fe₃O₄)—to predict their transport in adult mice’s brain under magnetic targeting. The simulation was validated by in vivo results by comparing the bioavailability of nanoparticles in different brain regions. Under a non-magnetic field, simulations revealed a capture efficiency of around 10.5% for all three types of nanoparticles, with size-dependent patterns favoring smaller sizes. With the presence of a magnetic field, MOF-Fe3O4 demonstrated the highest capture efficiency with “single magnet” at 11.19%, while Au-SPIO in “linear Halbach array” and MOF-Fe₃O₄ in “circular Halbach array” layouts reached 10.9%. Finally, we demonstrated high biocompatibility for all three nanocarriers, with no toxicity for Au-SPIO and MOF-Fe₃O₄ at 40 µg/mL and for HGNS-SPIO at 20 µg/mL. Effective cell uptake was also observed for all three nanocarriers. This comprehensive study addresses critical knowledge gaps, providing insights into the dynamics of magnetic nanocarrier transport within the brain and paving the way for highly effective, personalized therapies for neurological disorders.