title: Application of RPMI 2650 nasal cell model to a 3D printed apparatus for the testing of drug deposition and permeation of nasal products.
abstract: The aim of this study was to incorporate an optimized RPMI2650 nasal cell model into a 3D printed model of the nose to test deposition and permeation of drugs intended for use in the nose. The nasal cell model was optimized for barrier properties in terms of permeation marker and mucus production. RT-qPCR was used to determine the xenobiotic transporter gene expression of RPMI 2650 cells in comparison with primary nasal cells. After 14days in culture, the cells were shown to produce mucus, and to express TEER (define) values and sodium fluorescein permeability consistent with values reported for excised human nasal mucosa. In addition, good correlation was found between RPMI 2650 and primary nasal cell transporter expression values. The purpose-built 3D printed model of the nose takes the form of an expansion chamber with inserts for cells and an orifice for insertion of a spray drug delivery device. This model was validated against the FDA glass chamber with cascade impactors that is currently approved for studies of nasal products. No differences were found between the two apparatus. The apparatus including the nasal cell model was used to test a commercial nasal product containing budesonide (Rhinocort, AstraZeneca, Australia). Drug deposition and transport studies on RPMI 2650 were successfully performed. The new 3D printed apparatus that incorporates cells can be used as valid in vitro model to test nasal products in conditions that mimic the delivery from nasal devices in real life conditions.
authors.affiliation: Graduate School of Health - Pharmacy, University of Technology Sydney, 15 Broadway, Ultimo, NSW 2007, Australia.
authors.forename: Michele
authors.initials: M
authors.lastname: Pozzoli
authors.affiliation: Respiratory Technology, The Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, University of Sydney, 431 Glebe Point Road, Glebe, NSW 2037, Australia.
authors.forename: Hui Xin
authors.initials: HX
authors.lastname: Ong
authors.affiliation: Concord Repatriation General Hospital, Sydney Medical School-Concord Clinical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: Lucy
authors.initials: L
authors.lastname: Morgan
authors.affiliation: Graduate School of Health - Pharmacy, University of Technology Sydney, 15 Broadway, Ultimo, NSW 2007, Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Sukkar
authors.affiliation: Respiratory Technology, The Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, University of Sydney, 431 Glebe Point Road, Glebe, NSW 2037, Australia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
authors.affiliation: Respiratory Technology, The Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, University of Sydney, 431 Glebe Point Road, Glebe, NSW 2037, Australia.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
authors.affiliation: Graduate School of Health - Pharmacy, University of Technology Sydney, 15 Broadway, Ultimo, NSW 2007, Australia; Department of Pharmacy, University of Parma, 27A, Parco area delle Scienze, Parma 43124, Italy. Electronic address: fabio.sonvico@unipr.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Sonvico
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D003470:Culture Media; D019793:Fluorescein / Q000493:pharmacokinetics; D006801:Humans; D008854:Microscopy, Electron; D008954:Models, Biological; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066330:Printing, Three-Dimensional / Q000295:instrumentation*; D015262:Xenobiotics / Q000493:pharmacokinetics
chemical_list: D002352:Carrier Proteins; D003470:Culture Media; D015262:Xenobiotics; D019793:Fluorescein
keywords: 3D printing; Air Liquid Interface; Deposition; Dissolution; Mucus; Nasal permeation; Permeation; Primary nasal cell; RPMI 2650; Transporter expression