TY - JOUR
T1 - A Novel Preparation Technique for Human Nasal Respiratory Mucosa to Disclose Its Glycosylation Pattern for Bioadhesive Drug Delivery.
AU - Gausterer, Julia Clara
AU - Schlager, Michael
AU - Ahmadi, N.
AU - Nieratschker, M.
AU - Dahm, V.
AU - Wirth, Michael
AU - Arnoldner, Christoph
AU - Honeder, Clemens
AU - Gabor, Franz
N1 - Funding Information:
Open Access Funding by the University of Vienna.
Funding Information:
Christoph Arnoldner and Clemens Honeder receive funding from MED-EL Corporation, Innsbruck, Austria. MED-EL Corporation had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. For the remaining authors no conflicts of interest were declared.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/3/17
Y1 - 2023/3/17
N2 - To shed some light on glycotargeting as a potential strategy for nasal drug delivery, a reliable preparation method for human nasal mucosa samples and a tool to investigate the carbohydrate building blocks of the glycocalyx of the respiratory epithelium are required. Applying a simple experimental setup in a 96-well plate format together with a panel of six fluorescein-labeled lectins with different carbohydrate specificities allowed for the detection and quantification of accessible carbohydrates in the mucosa. As confirmed by binding experiments at 4 °C, both quantitatively by fluorimetry and qualitatively by microscopy, the binding of wheat germ agglutinin exceeded that of the others by 150% on average, indicating a high content of N-acetyl-D-glucosamine and sialic acid. Providing energy by raising the temperature to 37 °C revealed uptake of the carbohydrate-bound lectin into the cell. Moreover, repeated washing steps during the assay gave a slight hint as to the influence of mucus renewal on bioadhesive drug delivery. All in all, the experimental setup reported here for the first time is not only a suitable approach to estimating the basics and potential of nasal lectin-mediated drug delivery but also meets the needs for answering a broad variety of scientific questions involving the use of ex vivo tissue samples.
AB - To shed some light on glycotargeting as a potential strategy for nasal drug delivery, a reliable preparation method for human nasal mucosa samples and a tool to investigate the carbohydrate building blocks of the glycocalyx of the respiratory epithelium are required. Applying a simple experimental setup in a 96-well plate format together with a panel of six fluorescein-labeled lectins with different carbohydrate specificities allowed for the detection and quantification of accessible carbohydrates in the mucosa. As confirmed by binding experiments at 4 °C, both quantitatively by fluorimetry and qualitatively by microscopy, the binding of wheat germ agglutinin exceeded that of the others by 150% on average, indicating a high content of N-acetyl-D-glucosamine and sialic acid. Providing energy by raising the temperature to 37 °C revealed uptake of the carbohydrate-bound lectin into the cell. Moreover, repeated washing steps during the assay gave a slight hint as to the influence of mucus renewal on bioadhesive drug delivery. All in all, the experimental setup reported here for the first time is not only a suitable approach to estimating the basics and potential of nasal lectin-mediated drug delivery but also meets the needs for answering a broad variety of scientific questions involving the use of ex vivo tissue samples.
KW - glycotargeting
KW - intranasal drug delivery
KW - lectins
KW - mucoadhesion
KW - WGA
UR - https://www.scopus.com/pages/publications/85151320766
U2 - 10.3390/pharmaceutics15030973
DO - 10.3390/pharmaceutics15030973
M3 - Article
VL - 15
JO - Pharmaceutics
JF - Pharmaceutics
IS - 3
M1 - 973
ER -