In vitro Nasal Cell Culture Systems for Drug Transport Studies

Abstract

− Growing interest in the nasal route as a drug delivery system calls for a reliable in vitro model which is crucial for efficiently evaluating drug transport through the nasal cells. Various in vitro cell culture systems has thus been developed to displace the ex vivo excised nasal tissue and in vivo animal models. Due to species difference, results from animal studies are not sufficient for estimating the drug absorption kinetics in humans. However, the difficulty in obtaining reliable human tissue source limits the use of primary culture of human nasal epithelial cells. This shortage of human nasal tissue has therefore prompted studies on the "passage" culture of nasal epithelial cells. A serially passaged primary human nasal epithelial cell monolayer system developed by the air-liquid interface (ALI) culture is known to promote the differentiation of cilia and mucin gene and maintain high TEER values. Recent studies on the in vitro nasal cell culture systems for drug transport studies are reviewed in this article.

Nerve Growth Factor Biodelivery: A Limiting Step in Moving Toward Extensive Clinical Application?

“…In humans, this mucosa covers 10% of the total surface area, while in rodents, the most widely used species for intranasal administration studies, it can constitute up to 50% of the total area. This is an important aspect, because results obtained from animal models do not always correlate with those of humans, a discrepancy which probably comes from an insufficient consideration of the anatomical and physiological differences between the respective nasal cavities (Cho et al, 2010). Rodents are more widely used for preliminary nose-to-brain drug absorption studies, while rabbits and dogs are used for pharmacokinetic studies.…”

Development of a Novel ex vivo Nasal Epithelial Cell Model Supporting Colonization With Human Nasal Microbiota

“…Although improved, primary cell culture can pose challenges due to limits on the number of times the cultures can be passaged before senescence. This necessitates repeated collection of tissue from donors which can introduce biologic variability due to genetic differences or temporal variability in sample collection (Cho et al, 2010; Haghi et al, 2014; Papazian et al, 2016).…”

“…Finally, immortalized nasal and respiratory cell lines are available, such as the human nasal squamous cell carcinoma derived RPMI2650, the SV40-transformed bronchial cell line 16HBE14o- and the human lung adenocarcinoma derived Calu-3, that provide ample standardized and reproducible respiratory cell cultures. Unfortunately, these cell lines exhibit genetic and phenotypic discrepancies compared to primary cells, limiting in situ applicability of results (Cozens et al, 1994; Florea et al, 2003; Cho et al, 2010; Haghi et al, 2014; Papazian et al, 2016). Further, these cells fail to effectively model the nasal mucosa as they are primarily derived from deeper respiratory tract tissues.…”

“…Further, these cells fail to effectively model the nasal mucosa as they are primarily derived from deeper respiratory tract tissues. Despite the differences, utilization of immortalized respiratory cell cultures with conserved physiologic characteristics of interest proves useful in predicting in situ outcomes (Florea et al, 2003; Cho et al, 2010; Haghi et al, 2014; Papazian et al, 2016).…”

Primary Air–Liquid Interface Culture of Nasal Epithelium for Nasal Drug Delivery

“…Effective evaluation of nasal drug delivery systems requires a reliable in vitro or in vivo model. In vivo animal models and ex vivo excised human or animal tissue models are currently used as standards to study nasal drug delivery due to methodological and ethical limitations associated with human samples . However, these models have several limitations in terms of species differentiation between animals and humans as well as ethical and regulatory consideration associated with experimental animal use.…”