No abstract

Inhaled aerosols are absorbed across the oral cavity, respiratory tract, and gastrointestinal tract. The absorption across the oral cavity, which is one of the exposure routes, plays an important role in understanding pharmacokinetics and physiological effects. After aerosol exposure from e-cigarettes, tissue viability studies, morphological observation, and chemical analyses at the inner and outer buccal tissues were performed using organotypic 3D in vitro culture models of the buccal epithelium to better understand the deposition and absorption on the inner and outer buccal tissues. The aerosol exposures did not affect the tissue viability and had no change to the tissue morphology and structure. The deposition ratio at the buccal tissue surface is relatively low. This shows that majority of aerosol transfers to the airway tissues. The distribution from the inner tissue to the outer tissue has selectivity among various compounds, depending on the affinity with the liquid crystal structure of phospholipids and glucosylceramide. Although nicotine absorption in the aqueous solution was well known to increase as the unprotonated state of nicotine increased, the nicotine absorption after the aerosol exposure is irrelevant to the protonated–unprotonated state. Furthermore, the results showed that half of nicotine that adhered to the oral cavity transferred to the inner tissue via the oral epithelium and the other half transferred to the gastrointestinal tract accompanying multiple executions of swallowing, while majority of the water-soluble compounds with the hydroxyl group such as propylene glycol and benzoic acid that adhered to the oral cavity were eluted with the saliva and transferred to the gastrointestinal tract by swallowing.

Cigarette smoke (CS) is a risk factor contributing to lung remodeling in chronic obstructive pulmonary disease (COPD). COPD is a heterogeneous disease because many factors contribute in varying degrees to the resulting airflow limitations in different regions of the respiratory tract. This heterogeneity makes it difficult to understand mechanisms behind COPD development. In the current study, we investigate the regional heterogeneity of the acute response to CS exposure between large and small airways using in vitro three-dimensional (3D) cultures. We used two in vitro 3D human airway epithelial tissues from large and small airway epithelial cells, namely, MucilAir™ and SmallAir™, respectively, which were derived from the same single healthy donor to eliminate donor differences. Impaired epithelial functions and altered gene expression were observed in SmallAir™ exposed to CS at the lower dose and earlier period following the last exposure compared with MucilAir™. In addition, severe damage in SmallAir™ was retained for a longer duration than MucilAir™. Transcriptomic analysis showed that although well-known CS-inducible biological processes (i.e. inflammation, cell fate, and metabolism) were disturbed with consistent activity in both tissues exposed to CS, we elucidated distinctively regulated genes in only MucilAir™ and SmallAir™, which were mostly related to catalytic and transporter activities. Our findings suggest that CS exposure elicited epithelial dysfunction through almost the same perturbed pathways in both airways; however, they expressed different genes related to metabolic and transporter activities in response to CS exposure which may contribute to cytotoxic heterogeneity to the response to CS in the respiratory tract.