Molecular weight-dependent hyaluronic acid permeability and tight junction modulation in human buccal TR146 cell monolayers

The oral route is considered an attractive method for drug delivery, as it avoids the hepatic and intestinal first-pass metabolism processes. Hyaluronic acid (HA) beneficial effects to the human body include anti-aging and wound healing but its effects on oral barrier integrity and mechanical function have not yet been investigated. In this study, we analyzed oral barrier integrity and the paracellular pathway of HA transportation in TR146 cell monolayers during and after permeation and using low molecular weight HA (LMW-HA, <100 kDa) and high molecular weight HA (HMW-HA, >500 kDa). Cytotoxicity assays in TR146 cells revealed that neither LMW-HA or HMW-HA altered cell viability at concentrations <0.5 % during 24 h of treatment. HA-treated TR146 cell monolayers showed enhanced oral barrier integrity and reduced apparent permeability of fluorescein. Moreover, HA significantly increased tight junction (TJ)-related genes expression, including ZO-2, marvelD3, cingulin, claudin-1, claudin-3, and claudin-4 expression. Overall, the results of the present study indicate that HA can permeate across the oral barrier and enhance oral barrier function via the upregulated expression of TJ-related genes.