Nasal drug delivery: An in vitro characterization of transepithelial electrical properties and fluxes in the presence or absence of enhancers

Abstract

The study of the mechanisms of nasal drug absorption and factors affecting nasal drug absorption have been studied in vivo, but to date lack a simple, effective in vitro model system. We describe the use of Ussing chambers to study the transport of substances across, and the effect of chemicals on nasal mucosal tissue. Sheep nasal mucosa mounted in an Ussing chamber maintained viability for up to 8 hours as determined by measuring the electrical properties of the tissue, response to ion transport modifiers and histological assessment. Inulin (0.01 m M), mannitol (0.01 m M). and propranolol (0.008 m M.) were transported from the mucosal (m) to the serosal (s) side of the tissue at rates of 0.079, 0.249 and 1.02 nmol/cm 2/h, respectively. Transport from s-to-m and m-to-s occurred at equivalent rates, consistent with a passive transport mechanism. The rate of transport of propranolol was directly proportional to concentration over a range of 0.008 to 0.8 m M. The bile salt, deoxycholate, added to the mucosal bathing solution at 1 %, caused an increase in transepithelial conductance and irreversible tissue damage (cell necrosis). At 0.1%, deoxycholate reversibly increased transepithelial conductance (absence of cell necrosis) and enhanced the transport of mannitol and inulin 10–20 fold. These results demonstrate that the Ussing chamber provides a useful technique to investigate the nasal transport of drugs and allows evaluation of the effects of absorption enhancers on both absorption and tissue integrity.