DDEL-20. Microrobotic Local Solid Drug Delivery in the Brain: First Preclinical Study of a 3D Neuronavigated System

Abstract Delivering solid drugs locally and precisely into deep brain regions remains a major challenge in neurosurgery. We developed an intracerebral microrobot capable of navigating brain parenchyma and releasing solid drug implants at multiple anatomically precise targets. This introduces a new paradigm of personalized treatment, enabling oncologists to deliver tailored drug loads to multiple and specific brain areas. Since 2017, we have conducted in vivo and ex vivo studies to assess the feasibility of this neuronavigated method. Preclinical studies included 17 hydrogel delivery trials and one simulated monkey operation using a 1.3 mm flexible delivery system, replicating stereotactic clinical procedures. Delivery performance was assessed via angle accuracy, radial distance to the microrobot, and surgical feasibility. Tracking tests involved 10 in vitro phantom trials and one in vivo ewe trial using a 1 mm ultrasound sensor. Both linear and curved trajectories were tested, and emitter-receiver distances were recorded for 3D trilateration-based localization. Successful delivery was achieved in 14 of 18 trials, validated by two neurosurgeons. In bench tests, multiple insertion angles were evaluated; best accuracy was achieved at 35° (3 trials), with radial distance of 3.96 ± 0.07 mm and angular insertion of 35.2° ± 0.8°. Tracking enabled real-time trajectory reconstruction across 25 positions, confirmed with in vivo CT imaging. This study presents the first proof of concept for a 3D neuronavigated microrobotic system capable of delivering solid drug implants into deep brain regions with sub-millimetric precision. It supports the feasibility of precise, multi-site local drug delivery in neuro-oncology. Future work will validate accuracy in cadaver studies, integrating tracking and delivery systems to demonstrate the targeting of human brain structures.