Oral Absorption across Organotypic Culture Models of the Human Buccal Epithelium after E-cigarette Aerosol Exposure

[Image: see text] 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.