Intranasal delivery is rapidly gaining attention as a viable route for central nervous system (CNS) therapeutics—but turning scientific promise into clinical reality remains a work in progress.
In the panel discussion “Nasal Formulation Strategies for CNS Delivery”, moderated by Vivek Gupta, Associate Professor, Pharmaceutical Sciences, St. John’s University, experts Carolyn Berg, VP Business Development Inhalation, Catalent; Deb Das, Sr Associate Director Formulation Development & Fellow, Bayer U.S. LLC; Laleh Golshahi, Associate Professor, Mechanical & Nuclear Engineering, Virginia Commonwealth University and CEO, 3D Inhale; and Sitaram Velaga, President & CEO, Kenox Pharmaceuticals shared insights on where the field stands today and what’s needed next.
Why the renewed interest?
Advances in nasal biology, pharmacokinetics and device engineering are converging to make nose-to-brain delivery more feasible. As Berg highlighted, intranasal delivery offers faster onset, improved patient convenience and the potential to bypass the blood-brain barrier—particularly valuable for acute and hard-to-treat CNS conditions.
Advances in nasal biology, pharmacokinetics and device engineering are converging to make nose-to-brain delivery more feasible. As Berg highlighted, intranasal delivery offers faster onset, improved patient convenience and the potential to bypass the blood-brain barrier—particularly valuable for acute and hard-to-treat CNS conditions.
Encouraging—but early—progress
While marketed products like ketamine and naloxone demonstrate the route’s viability, overall success rates remain modest. Das estimated success at ~10%, reflecting both the complexity and high-risk, high-reward nature of this space. Even limited success, however, can deliver significant clinical and commercial impact.
While marketed products like ketamine and naloxone demonstrate the route’s viability, overall success rates remain modest. Das estimated success at ~10%, reflecting both the complexity and high-risk, high-reward nature of this space. Even limited success, however, can deliver significant clinical and commercial impact.
Persistent challenges
- Anatomical variability: As Golshahi noted, differences between patients—and even within the same patient over time—can dramatically affect drug deposition and targeting.
- Targeting limitations: Consistently reaching the olfactory region remains difficult but is critical for effective nose-to-brain transport.
- Translational gaps: Preclinical models often fail to predict human outcomes due to anatomical differences, complicating development pathways.
Formulation & device interplay
Success depends on the interaction between drug, formulation and device. While advanced systems such as nanoparticles, gels and powders are being explored, simpler liquid formulations still dominate due to scalability, cost and regulatory familiarity. Velaga emphasised that drug-device combination strategies must be considered early in development.
Regulatory bottlenecks
A major barrier remains outdated regulatory guidance. With FDA nasal guidelines largely unchanged since 2007, developers face uncertainty—particularly when combining novel molecules with novel delivery systems. Both Berg and Velaga stressed the urgent need for clearer, modernised frameworks.
A major barrier remains outdated regulatory guidance. With FDA nasal guidelines largely unchanged since 2007, developers face uncertainty—particularly when combining novel molecules with novel delivery systems. Both Berg and Velaga stressed the urgent need for clearer, modernised frameworks.
What will unlock progress?
- More predictive in vitro and hybrid models
- Better understanding of dose translation and deposition-target relationships
- Greater alignment between industry, academia and regulators
Intranasal CNS delivery is approaching a critical inflection point. The science is advancing, interest is growing—but meaningful progress will depend on solving variability, improving translation and modernising regulation.
