Author:

Keywords:

human nasal cell culture, nasal drug transport, lectin binding, histochemical characterization, airway epithelium, culture models, in-vivo, transport, metabolism, caco-2, mucosa, delivery, monolayers, binding, Science & Technology, Life Sciences & Biomedicine, Pharmacology & Pharmacy, CULTURE MODEL, TRANSPORT, CACO-2, METABOLISM, DELIVERY, DIFFERENTIATION, BINDING, PERMEABILITY, SUITABILITY, MONOLAYERS, 1115 Pharmacology and Pharmaceutical Sciences, 3214 Pharmacology and pharmaceutical sciences

Abstract:

In this study, we characterized human nasal epithelium cultured on derivatized and fibrillar collagen matrices for in vitro drug absorption studies by microscopy/haematoxylin eosin staining, lectin binding and permeation studies. Cell-lectin interaction was investigated using concanavallin A (Con A) and wheat germ agglutinin (WGA). Model compounds for transport studies include atenolol, propranolol, rhodamine and dextrans (FD4, FD-40, FD-70). Haematoxylin eosin staining revealed differentiated cells with monolayer morphology up to 2 weeks in culture. The cell concentration dependently and reversibly bound Con A and WGA, without internalization (no significant difference between binding at 4degreesC and 37degreesC, p > 0.05). The lectin binding was inhibited by complimentary sugars [alpha-D- (+) mannose and N-acetyl-D-galactosamine for Con A and WGA, respectively. The apparent permeability coefficients (cm/s x 10(-6)) for propranolol. atenolol and rhodamine were 32.8 +/- 4.8, 0.35 +/- 0.0 and 0.50 +/- 0.1, respectively. The derivatized collagen membranes significantly impeded the permeability of dextrans. This study shows that human nasal epithelium grown on collagen is a potentially useful in vitro model for nasal drug absorption studies.