Integrated aerosol deposition and epithelial transport in intranasal antiemetic dry powders.

Abstract

Intranasal dry powder delivery offers a non-invasive route for rapid systemic drug absorption and may be particularly beneficial for antiemetic therapy when oral administration is compromised. However, conventional in vitro tools typically assess aerosol deposition or epithelial permeability in isolation, limiting their ability to discriminate formulation-dependent transport behaviour. Two spray-dried formulations, differing only in the presence or absence of a non-ionic surfactant, were characterised for physicochemical properties and aerosol performance, followed by biological evaluation using an air liquid interface (ALI) RPMI-2650 nasal epithelial model. Aerosol delivery was performed using a nasal powder device coupled to a modified expansion chamber and cascade impactor, enabling direct deposition onto epithelial cell layers. Cytocompatibility, epithelial barrier integrity, and transepithelial drug transport were assessed alongside quantitative mass balance. Both formulations exhibited comparable solid-state properties, high emitted-dose reproducibility, and similar regional nasal deposition profiles. Neither formulation induced cytotoxicity nor disrupted epithelial barrier integrity, as evidenced by unchanged transepithelial electrical resistance and paracellular permeability. Despite similar deposition behaviour, the surfactant-containing formulation demonstrated faster initial transport and consistently higher transepithelial transport trends, without evidence of barrier compromise. These differences are consistent with formulation-dependent processes following deposition, such as differences in surface wetting and dissolution behaviour at the air-liquid interface. Overall, this study demonstrates that aerosol deposition alone may not fully predict epithelial transport for intranasal dry powders. The integrated deposition-transport platform provides a robust in vitro tool for formulation screening and optimisation, supporting the development of intranasal antiemetic therapies and other nasal drug products requiring rapid and reliable systemic delivery.