Sr. Associate Director, Global R&D & Science Fellow Bayer Healthcare LLC Morristown, New Jersey
The development of robust and predictive in vitro models for nose-to-brain drug delivery remains a critical challenge, particularly for therapeutics which cannot cross the blood–brain barrier (BBB) unaided. In such instances, understanding the nerve-mediated pathways - especially via the olfactory region of the nose becomes essential. Current strategies involve integrated systems such as co-culture models using primary nasal epithelial cells (e.g., RPMI 2650) with neuronal cells may simulating neuronal transport mechanisms. Emerging technologies such as microfluidic “nose-on-a-chip” systems and 3D bio-printed constructs allow dynamic assessment of airflow, mucociliary clearance, drug permeation, and toxicity. Furthermore, novel 3D hydrogel models incorporating immunological, glial, and neurovascular elements (Stanton et al.2024), offer in vivo-like features including neuronal signaling and barrier integrity, which are vital for evaluating nerve-specific uptake. Together, these complementary models represent powerful preclinical tools to optimize and de-risk intranasal drug formulations prior to advancing into in vivo studies.
Learning Objectives:
Design integrative approaches for advanced & predictive in vitro models for neuron-mediated uptake and transport of drugs to brain through nasal delivery, focusing on drugs which doesn't cross BBB unaided.
Advance the field of nose to brain delivery of a variety of drug molecules, including small molecules and biologics, by rapidly screening drug substances as well as finished formulations.
Mechanistically study the uptake mechanisms of nose to brain pathways and how advanced formulations can enable and/or enhance bioavailability in brain delivered via nose
Understand the toxicological implications of advanced formulations in vitro and thereby optimize the dose and/or formulation excipients using in vitro methods