Targeting the Ischemic Brain: Polymeric Nanoparticles as Next‐Generation Therapeutics

ABSTRACT Ischemic stroke is caused by blood flow obstruction to the brain, leading to brain cell death, which is associated with long‐term morbidity, socioeconomic concerns, and mortality. It is also one of the major causes of mortality worldwide, as the ischemic stroke death rates, just in a month's case, were from 4.8% to 37.6% globally. Still, an effective treatment strategy for ischemic stroke has not been developed due to its complex pathophysiology, which includes excitotoxicity, oxidative stress, and inflammation. These factors are interlinked with one another, which makes drug development more challenging. Current treatment methods for ischemic stroke include recombinant tissue plasminogen activator (rtPA) and endovascular thrombectomy (EVT), which have limitations such as a limited therapeutic window and complex procedure, respectively. Nanoparticles have gained importance due to their ability to provide sustained drug release, improved bioavailability, and targeted delivery. Among these, polymeric nanoparticles (P‐NPs) demonstrate enhanced therapeutic performance, with studies reporting significant infarct volume reduction (up to ~40%–70%), improved drug release efficiency (> 80%–90% under stimuli‐responsive conditions), and increased BBB uptake (2–3‐fold in ligand‐mediated systems). Their structural versatility enables efficient drug encapsulation, controlled release, and targeted delivery across the blood–brain barrier. This review discusses the pathophysiology of ischemic stroke, recent advancements in nanoparticle‐based systems, and the role of polymeric nanoparticles in improving therapeutic outcomes.