In-vitro nasal drug delivery studies: comparison of derivatised, fibrillarand polymerised collagen matrix-based human nasal primary culture systems for nasal drug delivery studies

The aim of this study was to establish a Collagen matrix-based nasal primar y culture system for drug delivery studies. Nasal epithelial cells were cul tured on derivatised (Cellagen membrane CD-24), polymerised (Vitrogen gel) and fibrillar (Vitrogen film) Collagen substrata. Cell morphology was asses sed by microscopy. The cells were further characterised by measurement of c iliary beat frequency (CBF), transepithelial resistance (TER), permeation o f sodium fluorescein, mitochondrial clehydrogenase (MDH) activity and lacta te dehydrogenase (LDH) release upon cell exposure to sodium tauro-24, 25 di hydrofusidate (STDHF). Among the three Collagen substrata investigated, the best epithelial differentiated phenotype (monolayer with columnar/cuboidal morphology) occurred in cells grown on Cellagen membrane CD-24 between day 4 and day 11. Cell culture reproducibility was better with Cellagen membra ne CD-24 (90 %) in comparison with Vitrogen gel (70 %) and Vitrogen film (< 10 %). TER was higher in cells grown on Vitrogen gel than on Cellagen memb rane CD-24 and Vitrogen film. The apparent permeability coefficient (P-app x 10(-7)cm s(-1)) of sodium fluorescein in these conditions was 0.45 +/- 0. 08 (Vitrogen gel) and 1.91 +/- 0.00 (Cellagen membrane CD-24). Except for L DH CBF and cell viability were comparable for all the substrata. Based on M DH activity, LDH release, release, CBF, TER and permeation studies, Cellage n membrane CD-24- and Vitrogen gel-based cells were concluded to be functio nally suitable for in-vitro nasal drug studies. Vitrogen film-based culture s may be limited to metabolism and cilio-toxicity studies.