Intranasal Nose-to-Brain Delivery: An Alternative Approach for Biologics in CNS Disorder Therapy

Central nervous system (CNS) disorders remain among the most challenging diseases to treat due to the restrictive nature of the blood–brain barrier (BBB), which severely limits the therapeutic efficacy of systemically administered biologics. Intranasal nose-to-brain delivery has emerged as a promising, non-invasive alternative route that enables direct transport of therapeutic agents to the brain via the olfactory and trigeminal neural pathways, bypassing the BBB. This approach offers significant advantages for biologics, including improved brain bioavailability, rapid onset of action, reduced systemic exposure, and enhanced patient compliance. Recent advances in formulation strategies such as nano- and micro-carriers, mucoadhesive systems, in situ gelling formulations, and enzyme-protective excipients have further enhanced the stability, targeting efficiency, and therapeutic performance of intranasally delivered biologics. This presentation critically discusses the anatomical and physiological basis of nose-to-brain transport, mechanisms governing intranasal absorption, and key formulation and device considerations for effective CNS targeting. Additionally, current preclinical and clinical progress, therapeutic applications in neurodegenerative and neurological disorders, and existing challenges related to mucociliary clearance, dose limitations, and safety are highlighted. Overall, intranasal nose-to-brain delivery represents a viable and evolving platform for the targeted administration of biologics in CNS disorder therapy, with strong potential for future clinical translation.

Dr.Niharika is working as an Associate Professor at Metro College of Health Sciences and Research, Greater Noida. She is Ph.D., and M.Pharm in Pharmaceutics, and has 7 years of teaching and research experience. She has 10 years of teaching experience with a diploma, bachelor and postgraduate students. She is having a total of  40 publications in international journals, and many of her articles are indexed in Scopus and SCI journals. During her Ph.D. she worked on ‘Design and characterization of an Acrylic Pressure sensitive adhesive-based Transdermal therapeutic system which she has appreciated by the Department of Polymer Sciences, IIT Kharagpur. Her area of interest is Transdermal Drug delivery and gastroretentive drug delivery