Intranasal administration nanosystems for brain-targeted drug delivery

The existence of the blood-brain barrier (BBB) restricts the entry of drugs from the circulation into the central nervous system (CNS), which severely affects the treatment of neurological diseases, including glioblastoma, Parkinson's disease (PD), and Alzheimer's disease (AD). With the advantage of bypassing the BBB and avoiding systemic distribution, intranasal administration has emerged as an alternative method of delivering drugs to the brain. Drug delivery directly to the brain using intranasal nanosystems represents a new paradigm for neurological disease treatment because of its advantages in improving drug solubility and stability in vivo, enabling targeted drug delivery and controlled release, and reducing non-specific toxicity. And it has shown efficacy in animal models and clinical applications. Herein, this review describes the mechanisms of intranasal delivery of brain-targeted drugs, the properties of nanosystems for intranasal administration (e.g., liposomes, nanoemulsions, and micelles), and strategies for intranasal drug delivery to enhance brain-targeted drug delivery. Recent applications of nanosystems in intranasal drug delivery and disease treatment have been comprehensively reviewed. Although encouraging results have been reported, significant challenges still need to be overcome to translate these nanosystems into clinics. Therefore, the future prospects of intranasal drug delivery nanosystems are discussed in depth, expecting to provide useful insights and guidance for effective neurological disease treatment.