Intranasal nanotherapeutics for brain targeting and clinical studies in Parkinson's disease

Parkinson's disease (PD) is the second leading neurodegenerative disease globally, impacting the quality of life of millions of people. It is estimated that the treatment cost of PD in the USA can rise to 79 billion dollars by 2037. Limited drugs are approved by USFDA, which only provides symptomatic relief. Further, the drug efficacy is challenged due to low drug-brain concentration due to first-pass metabolism and blood-brain barrier (BBB). Intranasal drug administration can offer several advantages over systemic administration, providing efficient brain delivery. Nose-to-brain (N2B) drug delivery can enhance brain bioavailability, reduce enzymatic degradation, and reduce systemic adverse effects. However, due to poor absorption from the nasal mucosa, intranasal administration can be challenging for hydrophilic drugs. The drug mucociliary clearance, retention time, and nasal enzymatic degradation can also affect N2B drug delivery. Nanocarriers can enhance residence time, improve nasal permeation, increase brain uptake, and reduce enzymatic degradation. This review discusses the roles and applications of various N2B nanocarriers to treat PD effectively. Clinical trials of antiparkinson molecules is also covered. Lastly, safety aspects and prospects of potential nanotherapeutics for the effective treatment of PD are discussed.