Engineered Extracellular Vesicles As a New Delivery Platform for Migraine.

Nose-to-Brain Nanocarriers for Migraine Management: A Comprehensive Review of Drug Delivery Strategies and Translational Challenges.

Microneedle-mediated drug delivery systems for brain diseases.

Brain diseases pose a major global health challenge, with the blood-brain barrier (BBB) as the core obstacle for intracranial drug delivery. Microneedles, a minimally invasive technology, can bypass the BBB via intracranial implantation, nose-to-brain, trigeminal nerve, and transdermal systemic routes. This review covers the structural classification, biomaterials, and bypass BBB delivery mechanisms of brain-targeted microneedles. Using glioblastoma, Alzheimer's disease, and Parkinson's disease as models, we overview preclinical microneedle formulations and key signaling pathways, and establish a matching framework linking therapeutic targets, drugs, and microneedle types. We further analyze clinical translation bottlenecks including limited drug loading, unclear long-term biosafety, manufacturing challenges, and regulatory gaps, and propose future directions in technical innovation, standardized evaluation, and regulatory improvement. This work may guide the rational design and clinical translation of microneedle-mediated brain-targeted drug delivery systems.

Extracellular vesicles for Alzheimer’s disease therapy: mechanisms, engineering strategies, and clinical translation

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, remains a major global health challenge owing to its complex pathogenesis and the presence of the blood-brain barrier (BBB), which substantially limits the delivery of effective therapeutics to the brain. Extracellular vesicles (EVs), which exhibit favorable biocompatibility, low immunogenicity, and an intrinsic capacity to cross the BBB, have emerged as promising therapeutic agents and delivery platforms for AD. This review focuses on the therapeutic potential of EV-based interventions in AD and summarizes recent advances in EV-mediated modulation of AD-related pathological processes, including amyloid-β (Aβ) clearance, tau protein regulation, neuroinflammation suppression, oxidative stress attenuation, and synaptic repair. Although EV-based therapies offer notable advantages, such as targeted BBB penetration and reduced immunogenic responses, their clinical translation remains constrained by safety concerns, including off-target effects, dose-dependent toxicity, and potential disturbances in neuroplasticity. In addition, this review discusses EV engineering strategies aimed at regulating the gut-brain axis (GBA), enhancing brain targeting, and advancing clinical translation. EV-based therapeutic interventions should therefore be developed within a safety-oriented framework supported by rigorous short- and long-term toxicological evaluation. Overall, this review highlights the therapeutic promise of EVs for AD while underscoring the need for rational engineering, standardized characterization, and safety-centered translational strategies to ensure clinical feasibility.

Nanotechnology-based Approaches for Nose -to- Brain Delivery of Antipsychotics

Neuropsychiatric disorders are one of the major neurodegenerative disorders that affect people. These disorders could be treated effectively by targeting drugs to the brain and overcoming the blood-brain barrier (BBB). Nanotechnology has proven its worth in targeting and delivering drug molecules to the target site. Various nanocarrier formulations have been utilized tremendously to target drugs to the brain via the intranasal pathway and have shown significant results in treating the disorders, since this pathway has emerged as a promising non–invasive alternative way of directly offering the drug to the brain via the olfactory and trigeminal pathway, which also bypasses systemic circulation and the hepatic first- pass effects. Nanotherapeutic approaches enhance the bioavailability, biodegradability, and protection of drug molecules from enzymatic degradation in nanoformulations; that is, they prevent enzymatic degradation of the drug. Moreover, these nanostructures have customizable surface properties that enable controlled drug release, thereby increasing targeting efficiency and leading to sustained therapeutic action. The current review focuses on the intranasal route of administration and shows nano formulations are effectively delivered to the brain via this route. This review provides readers with an insight into how different nano-carrier-based formulations, such as polymeric-based nanoparticles, nano-lipid carriers, nano-emulsions, and solid lipid nanocarriers, enhance drug bioavailability, target affinity, and overcome first-pass metabolism, and also highlights the recent advancements and formulation approaches to optimize drug targeting to the brain in order to manage complex neurological disorders.

Nanomedicine for epilepsy: Expanding beyond conventional drug targets.

This discussion aims to inspire a reorientation of nanomedicine strategies toward precision therapy for epilepsy by highlighting how emerging nanomedicines are expanding the therapeutic target repertoire to include key non-neuronal nodes, with a focus on neuroinflammation and BBB repair.

Exosomes in brain diseases: Mechanisms, advances, and perspectives

The blood–brain barrier (BBB) remains a major biological obstacle limiting the effective delivery of therapeutics for central nervous system (CNS) disorders. Although conventional drug delivery approaches have achieved continuous advances, their clinical translation is frequently restricted by limited brain penetration, insufficient target specificity, and systemic adverse effects. Exosomes, endogenous extracellular vesicles (EVs) involved in intercellular communication, have emerged as promising candidates for CNS therapeutic delivery owing to their favorable biocompatibility, relatively low immunogenicity, and potential ability to interact with biological barriers. In this review, we first summarize the structural characteristics of the BBB and the mechanisms underlying exosome–BBB interactions and transport. We then discuss current strategies for exosome isolation, characterization, and engineering, highlighting how these approaches influence therapeutic performance and translational feasibility. Subsequently, we analyze recent advances in exosome-based therapies for major CNS disorders, including neurodegenerative diseases, brain tumors, and ischemic stroke, with emphasis on how distinct pathological environments guide the design of exosome cargos, targeting strategies, and functional modifications. Finally, we discuss key challenges associated with clinical translation, including manufacturing standardization, pharmacokinetic evaluation, safety assessment, and regulatory considerations. This review provides a pathology-driven and engineering-guided perspective for understanding the rational design and future development of exosome-based therapeutics for CNS disorders.