Abstract:
:An in vitro human nasal model was developed as a tool to study the local tolerability of nasal powder forms using excised nasal mucosa in a diffusion chamber. The suitability of this model was tested using Sandostatin (SMS) an octapeptide analog of somatostatin, as a reference drug enhanced by Avicel (microcrystalline cellulose) or lactose (100 mesh). The standard nasal spray vehicle was taken as a harmless control and 1% chenodeoxycholate (CDC) as a harmful control in terms of local tolerability. The extent of peptide permeation was determined by measuring SMS concentration in the receiving chamber. The labeling of SMS was detected by immunoperoxidase staining on cross sections. The local tolerability for all tested forms was assessed by histopathological examination and scanning electron microscopy. The apparent permeation coefficient allowed us to rank the absorption of the tested drug forms as Avicel > spray = lactose > 1%CDC. For all formulations, SMS was detected in the epithelium. No changes of the nasal mucosa could be observed with Avicel, lactose or nasal spray vehicle in the presence or absence of SMS. 1%CDC with or without drug showed an immediate destruction of the nasal epithelium. The validation of this in vitro model using human nasal mucosa will be further discussed as a tool for assessing the local tolerability of intranasally applied test substances.
journal_name
Cell Biol Toxicoljournal_title
Cell biology and toxicologyauthors
de Fraissinette A,Kolopp M,Schiller I,Fricker G,Gammert C,Pospischil A,Vonderscher J,Richter Fdoi
10.1007/BF00757627subject
Has Abstractpub_date
1995-10-01 00:00:00pages
295-301issue
5eissn
0742-2091issn
1573-6822journal_volume
11pub_type
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