Fucoidan-coated metal–organic framework nanoparticles for targeted delivery of nimodipine in subarachnoid hemorrhage-induced vasospasm

Abstract

Cerebral vasospasm following subarachnoid hemorrhage (SAH) is a major contributor to delayed cerebral ischemia (DCI). Although conventional nimodipine administration remains the standard therapy for cerebral vasospasm and DCI, its clinical utility is limited by rapid cerebrospinal fluid (CSF) clearance and dose-limiting systemic hypotension. To address these challenges, we developed a clot-targeted drug delivery platform for direct intrathecal infusion based on fucoidan-functionalized metal–organic framework (MOF) nanoparticles (Fu@UiO-67). Fu@UiO-67 features a bifunctional fucoidan coating that enables clot anchoring and diffusion-controlled drug release. In a rat SAH model, Fu@UiO-67 exhibited a 50-fold greater retention at the target neurovascular interface than non-coated nanoparticles. This site-specific retention effectively mitigated CSF washout, resulting in sustained therapeutic exposure and a four-fold increase in local drug bioavailability relative to bolus nimodipine. Consequently, Fu@UiO-67 demonstrated superior pharmacodynamic efficacy, achieving over 90% restoration of the vascular lumen-to-wall ratio, whereas intrathecal bolus administration of nimodipine resulted in limited recovery (65.1%). Taken together, these findings highlight Fu@UiO-67 as a promising and clinically translatable strategy for localized SAH treatment, maximizing site-specific therapeutic efficacy while minimizing systemic exposure to nimodipine.