Intracranial administration of surface modified PAMAM dendrimer migrates to the infarct area in the MCAo rat model of stroke.

Ischemic stroke induces hypoxia-driven neuroinflammation, leading to neuronal death and glial scar formation that hinders recovery. In this study, we evaluated Cy5.5-tagged generation 4 PAMAM dendrimer as a potential therapeutic delivery vector in a middle cerebral artery occlusion (MCAo) rat model. Primary astrocyte cultures confirmed GFAP expression and dendrimer uptake. Intracranial injections and in-vivo brain imaging revealed Cy5.5 localization in the brain. Immunohistochemistry revealed Cy5.5 localization near the infarct area as well as in astrocytes, neurons, and microglia. We did not observe any significant reduction in infarct volume nor observed behavioral alteration. These findings establish G4 90/10-Cy5.5 as an inert, a safe, biocompatible nanocarrier for targeted post-stroke therapeutic delivery.