Intranasal delivery route for neurodegenerative diseases: recent insights and future directions

Neurodegenerative diseases are increasingly significant causes of mortality and morbidity worldwide, particularly among the elderly. Despite their widespread prevalence, effective treatment options remain inadequate. A significant challenge contributing to this therapeutic gap is the impermeability of the blood-brain barrier to many drugs. Thus, developing new strategies to bypass this barrier and deliver therapeutic agents to the central nervous system (CNS) is crucial. The intranasal (IN) route has emerged as a promising approach in animal models of neurodegenerative diseases. This method of administration is gaining attention as a viable alternative for delivering various pharmacological agents, including proteins, miRNA, and oligonucleotides, to the CNS. It offers advantages over oral and intravenous routes. However, translating IN formulations from preclinical models to clinical practice presents several challenges. Assessing the adequacy of current clinical trials in evaluating IN delivery efficacy is crucial. Furthermore, the introduction of novel formulations such as nanoparticles sparks excitement for enhancing the effectiveness of IN drug administration compared to traditional free drug solutions. This review summarizes recent advancements in delivering therapeutic molecules to the CNS to treat neurodegenerative diseases. We explore critical strategies to overcome the blood-brain barrier obstacle, focusing on recent progress using the IN route as a potential avenue for effective neurodegenerative disease therapies. Additionally, we will delve into the preclinical studies that have provided the basis for the clinical trials conducted.