The nasal route for nose-to-brain drug delivery: advanced nasal formulations for CNS disorders

INTRODUCTION: The nasal route offers a feasible alternative to oral and/or parenteral administration, providing a noninvasive route to achieve nose-to-brain drug delivery involving the olfactory and trigeminal nerves, and facilitating local or systemic drug action. Conventional liquid nasal dosage forms have not managed to bridge the gaps of precise dosing and targeted central nervous system (CNS) delivery, while more sophisticated formulation approaches are being explored for brain targeting, aiming to enhance bioavailability and therapeutic efficacy. AREAS COVERED: This review focuses on preclinical and clinical evaluation of microemulsions, in-situ gels, nasal powders, and nanocarrier-based formulations. Key pharmacokinetic and pharmacodynamic findings are discussed to evaluate their potential and limitations in improving drug bioavailability and CNS targeting. The existing regulatory framework for approval of products for nose-to-brain drug delivery is also addressed and relative hurdles are discussed. EXPERT OPINION: While nasal drug delivery holds great promise for CNS therapeutics, key challenges remain, including formulation stability, mucosal permeability, patient adherence. Future research should prioritize improving targeting efficiency, overcoming mucociliary clearance, developing user-friendly pharmaceutical products. Personalized medicine and smart delivery systems could further enhance drug targeting and minimize side effects. Continued research and regulatory advancements are essential to fully realize nasal delivery's perspective in CNS therapeutics.