Abstract
Topical drug administration to the oral mucosa proves to be a promising treatment alternative for inflammatory diseases. However, disease-related changes in the cell barrier must be considered when developing such delivery systems. This study aimed at investigating the changes in the lining mucosa caused by inflammation and evaluating the consequences on drug delivery systems such as nanostructured lipid carriers (NLC). For this, TR146 cells were treated with inflammatory cytokines and bacterial components. Cell viability and integrity, reactive oxygen species (ROS), and interleukin (IL)-8 release were used as endpoints to assess inflammation. Translocation of phosphatidylserine, cytoskeletal arrangement, opening of desmosomes, and cell proliferation were examined. Transport studies with NLC were performed considering active and passive pathways. The results showed that IL-1ß and tumor necrosis factor α induced inflammation by increasing IL-8 and ROS production (22-fold and 2-fold). Morphologically, loss of cell–cell connections and formation of stress fibers and hyperplasia were observed. The charge of the cell membrane shifted from neutral to negative, which increased the absorption of NLC due to the repulsive interactions between the hydrophobic negative particles and the cell membrane on the one hand, and interactions with lipophilic membrane proteins such as caveolin on the other.
Highlights
The membrane integrity was comparable to the cell control with no significant alterations in the lactate dehydrogenase (LDH) release
Inflammatory diseases of the mouth, such as stomatitis and oral mucositis, are chronic conditions pathologically characterized by inflammation and epithelial lesions
Using human epithelial TR146 cells, it was found that cytokines, in particular IL-1ß and TNF-α, induced an inflammatory event in TR146 cells
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Oral health is an essential indicator of general health, well-being, and quality of life. Mechanical stress and chemical toxicants might change the homeostasis in the mouth leading to a number of conditions such as tooth decay, periodontal disease, stomatitis, cancer, oral mucositis, infections, xerostomia, and others. It is estimated that oral diseases affect 3.5 billion people worldwide and are among the fourth most common diseases in Europe, with annual costs of €79 billion [1,2]
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