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

Ong, Hui Xin; Jackson, Claire; Cole, Janice L.; Lackie, Peter M.; Traini, Daniela; Young, Paul M.; Lucas, Jane S.; Conway, Joy

doi:10.1021/acs.molpharmaceut.5b00852

Cited by 44 publications

(33 citation statements)

References 55 publications

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“…Human nasal epithelial cells were obtained from healthy volunteers free from respiratory tract infections for at least 4 weeks as previously described 19…”

Section: Culture and Differentiation Of Human Primary Nasal Epithelmentioning

confidence: 99%

Pollen exposure weakens innate defense against respiratory viruses

Gilles

Blume

Wimmer

et al. 2019

Allergy

101

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Background Hundreds of plant species release their pollen into the air every year during early spring. During that period, pollen allergic as well as non‐allergic patients frequently present to doctors with severe respiratory tract infections. Our objective was therefore to assess whether pollen may interfere with antiviral immunity. Methods We combined data from real‐life human exposure cohorts, a mouse model and human cell culture to test our hypothesis. Results Pollen significantly diminished interferon‐λ and pro‐inflammatory chemokine responses of airway epithelia to rhinovirus and viral mimics and decreased nuclear translocation of interferon regulatory factors. In mice infected with respiratory syncytial virus, co‐exposure to pollen caused attenuated antiviral gene expression and increased pulmonary viral titers. In non‐allergic human volunteers, nasal symptoms were positively correlated with airborne birch pollen abundance, and nasal birch pollen challenge led to downregulation of type I and ‐III interferons in nasal mucosa. In a large patient cohort, numbers of rhinoviruspositive cases were correlated with airborne birch pollen concentrations. Conclusion The ability of pollen to suppress innate antiviral immunity, independent of allergy, suggests that high‐risk population groups should avoid extensive outdoor activities when pollen and respiratory virus seasons coincide.

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“…Human nasal epithelial cells were obtained from healthy volunteers free from respiratory tract infections for at least 4 weeks as previously described 19…”

Section: Culture and Differentiation Of Human Primary Nasal Epithelmentioning

confidence: 99%

Pollen exposure weakens innate defense against respiratory viruses

Gilles

Blume

Wimmer

et al. 2019

Allergy

101

View full text Add to dashboard Cite

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“…These models feature a pseudostratified epithelial morphology, barrier properties, basal cells, mucus-producing goblet cells, and ciliated cells facilitating mucociliary clearance. [6][7][8][9]…”

mentioning

confidence: 99%

Investigation on Ciliary Functionality of Different Airway Epithelial Cell Lines in Three-Dimensional Cell Culture

Lodes

Seidensticker

Perniss

et al. 2020

Tissue Engineering Part A

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Three-dimensional respiratory tissue models have been generated using, for example, human primary airway epithelial cells (hAEC) or respective cell lines. To investigate ciliopathies, such as primary ciliary dyskinesia, the presence of functional kinocilia in vitro is an essential prerequisite. Since access to hAEC of healthy donors is limited, we aimed to identify a respiratory epithelial cell line that is capable to display functional kinocilia on at least 60% of the apical surface. Thus, we cultured four different human respiratory cell lines with human primary airway fibroblasts under airlift conditions, characterized the morphology, and analyzed ciliary function. Only one of the tested cell lines showed beating kinocilia; however, <10% of the whole surface was covered and ciliary beating was undirected. Positive control tissue models using hAEC and fibroblasts displayed expected directed ciliary beating pattern around 11 Hz. Our data show that the available cell lines are not suitable for basic and applied research questions whenever functional kinocilia are required and that, rather, hAEC-or human induced pluripotent stem cell-derived tissue models need to be generated.To study ciliopathies or Bordetella pertussis infection in vitro, three-dimensional respiratory tissue models with functional kinocilia covering at least 60% of the model's surface are mandatory. We cultured four respiratory cell lines on a fibroblastloaded biological scaffold and showed that none of them met this requirement. In contrast, primary airway cell-derived models sufficiently reflected the mucociliary phenotype. To further search for an alternative to primary respiratory cells, investigations on other cell lines should be conducted or even new cell lines have to be generated. IntroductionT hree-dimensional (3D) cell cultures of the respiratory epithelium/mucosa afford research on-for examplethe impact of airborne pollutants, host-pathogen interactions, and drug permeation. 1-5 As source for respiratory epithelial cells, primary cells, induced pluripotent stem cells (iPSC), or cell lines can be used. Both primary cells and iPSC provide the opportunity to generate personalized tissue models, for example, to study individual drug responses or drug efficacy. Moreover, they show a high in vitro-in vivo correlation. These models feature a pseudostratified epithelial morphology, barrier properties, basal cells, mucus-producing goblet cells, and ciliated cells facilitating mucociliary clearance. [6][7][8][9]

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“…As with immortalized cells, the ALI configuration is essential for the establishment of cell polarization. An interesting work underscored that the formation of tight junctions and the cilia beating were apparent 4 weeks after culture under ALI conditions (Ong et al, 2016). 4.1.3.2.…”

Section: In Vitro Modelsmentioning

confidence: 99%

How to characterize a nasal product. The state of the art of in vitro and ex vivo specific methods

Salade

Wauthoz

Goole

et al. 2019

International Journal of Pharmaceutics

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Nasal delivery offers many benefits over other conventional routes of delivery (e.g. oral or intravenous administration). Benefits include, among others, a fast onset of action, non-invasiveness and direct access to the central nervous system. The nasal cavity is not only limited to local application (e.g. rhinosinusitis) but can also provide direct access to other sites in the body (e.g. the central nervous system or systemic circulation). However, both the anatomy and the physiology of the nose impose their own limitations, such as a small volume for delivery or rapid mucociliary clearance. To meet nasal-specific criteria, the formulator has to complete a plethora of tests, in vitro and ex vivo, to assess the efficacy and tolerance of a new drug-delivery system. Moreover, depending on the desired therapeutic effect, the delivery of the drug should target a specific pathway that could potentially be achieved through a modified release of this drug. Therefore, this review focuses on specific techniques that should be performed when a nasal formulation is developed. The review covers both the tests recommended by regulatory agencies (e.g. the Food and Drug Administration) and other complementary experiments frequently performed in the field.

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

Cited by 44 publications

References 55 publications

Pollen exposure weakens innate defense against respiratory viruses

Pollen exposure weakens innate defense against respiratory viruses

Investigation on Ciliary Functionality of Different Airway Epithelial Cell Lines in Three-Dimensional Cell Culture

How to characterize a nasal product. The state of the art of in vitro and ex vivo specific methods

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