HCR.20.022 – Spatio-temporally controlled drug delivery in the brain: a new avenue for stroke treatment

Route: Health care research, sickness prevention and treatment

Cluster question: 083 How do neurological, psychiatric, and mental disorders arise, and how can we prevent, mitigate, or cure them?

Ischemic stroke is the major cause of adult disability in developed nations, affecting about 3% of the population. Many neuroprotective drugs have shown promising results in animal studies, but clinical trials in patients have all failed thus far. Most pharmacological treatments are administered systemically, but this has some key limitations: 1) many promising drugs cannot be applied at the dosage that would be necessary for effectively treating (peri-)lesional areas without severe side effects; 2) substances need to be able to cross the blood-brain barrier; 3) it is not possible to specifically target drug delivery to stroke-affected brain regions, at the time when drugs are most needed. To address this, we will develop a microfluidics-based device to release drugs in a spatio-temporally limited fashion to cortical areas only and at the same time monitor cortical activity to implement closed-loop drug delivery, i.e. not based on an a priori regime but on biophysical markers of neuronal health. The project will be organized in three phases. First, we will develop and test in vitro a biocompatible, microfluidics-based device for spatio-temporally limited drug delivery. Second, we will perform in vivo experiments in mice to test the device, verify whether our approach improves the efficacy of drug-based stroke treatments, and pilot the integration with methodologies to monitor neural activity. Third, we will develop a version of the device for human applications and perform preliminary validation tests. An ethical assessment on the implications of the device-patient interactions will be made. Our project will develop a new, personalized approach to address stroke, in which drug delivery is spatially focused on the extent of a patient�s ischemic lesion and temporally limited based on how brain tissue reacts to treatment. This will finally make it possible to develop successful pharmacological treatments for stroke.

Keywords

closed-loop interface, drug delivery, microfluidics, stroke

Other organisations

Amsterdam UMC, Saxion Hogeschool, Technische Universiteit Delft (TUD)

Submitter

Organisation University of Amsterdam (UvA)
Name Dr. U. (Umberto) Olcese
E-mail u.olcese@uva.nl