Challenges and progress in nose-to-brain drug delivery

Numerous diseases have been found to be associated with the central nervous system (CNS). The traditional oral and intravenous methods of treatment have several limitations, resulting in poor therapeutic outcomes for such illnesses. The intranasal (IN) route is a relatively simple and noninvasive pathway for rapid drug administration directly into the CNS. This route, known as the nose-to-brain (NtB) pathway, exploits brain and nasal cavity connectivity through olfactory and trigeminal nerves, circumventing systemic circulation. Administering drugs via this route can bypass the blood-brain barrier (BBB) and reduce the number of drug moieties distributed to nontarget organs, giving the advantages of minimal dose reduction, no systemic dilution, and avoiding first-pass hepatic metabolism. The NtB delivery system can achieve a higher brain/blood drug concentration ratio by several-fold and has been extensively studied to deliver drugs targeted for CNS disorders. Despite these advantages, delivering drugs to the CNS through the nasal cavity is challenging due to anatomical (access to the olfactory and trigeminal nerve), physiological (mucociliary clearance, nasal cavity environment), and formulation (drug loading, delivery volume, delivery efficiency) factors. Interdisciplinary research has been conducted to overcome these challenges. The pursuits in this field include better design of applicators to allow precise delivery of the dosage forms, the engineering of mucoretentive vehicles and materials to overcome nasal clearance, and utilization of different micro and nanocarriers to increase delivery efficiency and to provide protection for drug molecules susceptible to chemical or metabolic degradation. Moreover, 3D printing techniques have been employed to aid this delivery system’s future design and development. Promising progress has been made, pushing these novel technologies further down the research pipeline and clinical translation.