Nasal drug transport studies

Ethical issues as well as difficulty in obtaining enough human nasal tissue specimens have called for the need to use alternative in vitro and in vivo methods. Various in vivo animal models and in vitro excised tissue models have been described in the literature for nasal drug transport studies. However, due to the difficulty in both controlling the experimental conditions in in vivo animal models and obtaining intact excised tissue samples, in vitro cell culture models are also being actively developed. 

N. V. Chemuturi, P. Hayden, M. Klausner, and M. D. Donovan. Comparison of human tracheal/bronchial cell culture and bovine nasal respiratory explants for nasal drug transport studies. J Pharm Sci 94 1976-1985 (2005). 

Osth K, Grasjo J, Bjork E (2002) A new method for drug transport studies on pig nasal mucosa using a horizontal Ussing chamber. J Pharm Sci 91 1259-1273. 

Models for Nasal Drug Transport and Absorption Studies... 

Cultured nasal cells are reliable models for drug transport and metabolism studies, since they are known to express important biological features (e.g. tight junctions, mucin secretion, cilia, and various transporters), resembling those found in vivo systems. Moreover, easy control of experimental conditions as well as separation of the permeation step from the subsequent absorption cascade is also possible. A relatively simple primary culture condition using human nasal epithelial cells for in vitro drug transport studies has been established and applied in transport and metabolism studies of drugs. It is known that the culture condition and/or selection of culture media are critical in the recapitulation of well-differentiation features of in vivo nasal mucosal epithelium [46],... 

U. Werner and T. Kissel. In-vitro cell culture models of the nasal epithelium A comparative histochemical investigation of their suitability for drug transport studies. Pharm Res 13 978-988 (1996). 

Schmidt MC, Simmen D, Hilbe M, Boderke P, Ditzinger G, Sandow J, Lang S, Rubas W, Merkle HP (2000) Validation of excised bovine nasal mucosa as in vitro model to study drug transport and metabolic pathways in nasal epithelium. J Pharm Sci 89 396-407. 

Methods to determine ciliary beat frequency and mucociliary transport in vitro and in vivo have been extensively reviewed elsewhere [84,121], In general, in vivo methods are more reliable for ciliotoxicity studies than in vitro methods and are essential to confirm the safety of nasal drug formulations. However, in vitro methods are more suitable for the large number of screening studies required during formulation development [122],... 

Discussion of specific cell types characteristic of the epithelial cells along the respiratory tract and corresponding cell culture models for studying nasal and pulmonary drug transport are separated below, with generally more focus on the airway (tracheal and bronchial) epithelium and the alveolar epithelium. 

Excised nasal mucosae obtained from various animal species are tools frequently used to study nasal transport and metabolism ([53], Chap. 4). Maintaining the viability of the excised nasal tissues during the experimental period is crucial. Most studies were performed with epithelia excised from rabbits, bovine, sheep, and dogs tissues [54-57], This excised nasal tissue model has been shown to be well suited for studies on nasal permeation and metabolism of drugs. However, species differences in the activity of various enzymes found in human versus these animal nasal mucosae have become an important issue. 

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