Abstract
Nasal route drug administration for local and systemic delivery of many therapeutics has received attention because the nasal cavity is highly vascularized and provides a large surface area for drug absorption. However, nasal mucosa exhibits limited permeability to polar molecules. In this study, we developed a novel method for improving absorption efficiency of polar drugs by applying hypergravity. RPMI 2650 cells and primary human nasal epithelial cells were exposed three times to a 20 min hypergravitational condition (10 × g) with a 20 min rest period after each exposure. The applied hypergravity induced a decrease in transepithelial electrical resistance without significant loss of cellular metabolic activity, and cellular permeability of fluorescein sodium salt (MW 376 Da; NaFI) and FITC-labeled dextran (average MW 4,000 Da; FD-4) increased by 19% and 16%, respectively. Immunostaining and RT-qPCR results demonstrated that hypergravity conditions affected cytoskeletal structures and tight junctions, leading to weakening of the cell barrier function and increasing the cellular permeability of polar molecules. Our results indicate that hypergravity could be used as a new strategy for enhancing the efficiency of drug absorption via the nasal route.
Highlights
Needle insertions cause pain, result in scar tissues in patients who suffer from chronic diseases, and induce needle phobia in child patients, the demand for needle-free drug delivery techniques has been increasing
We investigated the effects of the applied hypergravity on transepithelial electrical resistance (TEER), cell proliferation, cellular permeability, cytoskeletal structures, and gene expressions
A cell counting kit-8 (CCK-8) assay was used to investigate the hypergravitational effect on the metabolic activity of RPMI 2650 cells (Fig. 2)
Summary
Result in scar tissues in patients who suffer from chronic diseases, and induce needle phobia in child patients, the demand for needle-free drug delivery techniques has been increasing. Several strategies have been developed to improve the cellular transport rate of polar drugs, and many strategies involve absorption-promoting agents such as surfactants, bile salts (or their derivatives), phospholipids, cyclodextrins, and cationic polymers[16,17,18,19,20]. Those enhancers have toxic potentials such as the capability to cause severe morphological alterations, significant membrane damage in the epithelium, and inhibition of mucociliary transport[21,22]. Cytoskeletal structures were altered and gene expression levels of junctional proteins and β-actin were upregulated following exposure to hypergravity
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