Nasal Drug Delivery Systems and Epithelial Modeling

Nasal administration has emerged as a strategic non-invasive route for both local therapy and systemic drug absorption, with particular promise for rapid onset of action and direct nose-to-brain transport. The nasal cavity presents a highly vascularised mucosal surface and access to the olfactory region, bypassing the blood–brain barrier for central nervous system targeting. However, effective delivery is challenged by mucociliary clearance, enzymatic barriers and tight epithelial junctions. Advances in formulation science—encompassing powders, sprays, gels and nanoparticles—are complemented by innovations in delivery devices that optimise aerosol characteristics and regional deposition. To predict and optimise in vivo performance, sophisticated in vitro and ex vivo epithelial models have been developed. These range from traditional tumour-derived cell lines cultured at an air–liquid interface to primary-cell co-cultures, three-dimensional bioprinted constructs and microfluidic “mucosa-on-chip” platforms. Such models recreate mucus secretion, ciliary motility and epithelial barrier properties, enabling concurrent assessment of deposition, permeability, cytotoxicity and microbial interactions. Collectively, these systems inform formulation design, enhance mechanistic understanding of transport pathways and reduce reliance on animal testing, thereby accelerating translation of nasal therapeutics for global applications in pain management, vaccination, neurodegenerative disorders and emergency care.

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Nasal Drug Delivery Systems and Epithelial Modeling publication trend

The graph below shows the total number of articles in nasal drug delivery systems and epithelial modeling across all publications each year (not limited to Nature Index journals).

Technical terms

Air–liquid interface (ALI): Culture condition where epithelial cells are exposed to air on their apical surface and medium below to promote differentiation and barrier formation.

Transepithelial electrical resistance (TEER): Quantitative measure of ionic conductance across a cell layer used to assess epithelial barrier integrity.

Poly(lactic-co-glycolic acid) (PLGA): Biodegradable polymer commonly employed to fabricate nanoparticles for controlled and targeted drug delivery.

Cell-penetrating peptide (CPP): Short peptide sequence that facilitates translocation of therapeutic molecules across cellular membranes.

Nasal cast model: Three-dimensional replica of the human nasal cavity used to simulate and quantify regional deposition of aerosolised formulations.

References

1. A Cell-Based Nasal Model for Screening the Deposition, Biocompatibility, and Transport of Aerosolized PLGA Nanoparticles. Molecular Pharmaceutics (2024).
2. A Modified Cell-Penetrating Peptide Enhances Insulin and Oxytocin Delivery across an RPMI 2650 Nasal Epithelial Cell Barrier In Vitro. Pharmaceutics (2024).
3. The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 2—Advanced Microfluidic Nasal In Vitro Model for Drug Absorption Testing. Pharmaceutics (2023).