A Review of Nanoparticle‐Based Astrocyte Modulation in CNS Disorders: Evaluating the Underexplored Potential of Intranasal Delivery

Central nervous system (CNS) disorders pose significant therapeutic challenges due to the blood–brain barrier (BBB), enzymatic degradation, and low drug bioavailability. Astrocytes, once considered passive supporting cells, are now being recognized as central regulators of neuroinflammation and neurodegeneration. Nanoparticles capable of targeting astrocytes offer a promising strategy for modulating these pathological processes. This review critically evaluates the current landscape of astrocyte‐modulating nanotherapeutics across CNS diseases, identifying both mechanistic strengths and translational gaps. Despite the success of nose‐to‐brain drug delivery as a noninvasive route to bypass the BBB, most nanoparticle‐based studies neglect this pathway, and no FDA‐approved intranasal (IN) CNS formulations to date specifically target astrocytes. This review highlights this disconnect by analyzing both investigational nanoformulations and approved IN therapeutics, revealing a missed opportunity in CNS‐targeted therapy. Bridging this gap, by uniting the astrocyte specificity of engineered nanoparticles with the direct CNS access of IN delivery, presents a compelling frontier for the next generation of neurotherapeutics.