Accumulation of Topical Naproxen by Cultured Oral Epithelium

Abstract

Topically administered non-steroidal anti-inflammatory drugs (NSAIDs) inhibit periodontal bone loss, but little is known about the mechanism by which they penetrate oral epithelium. Active transporters could potentially play a role in this process. In this study, we used a cell line derived from oral epithelium to investigate a role for transporters and to characterize conditions that enhance epithelial penetration. Using fluorescence to monitor uptake, we demonstrated that SCC-25 cell monolayers transport naproxen with a Michaelis constant (K_m) and maximum velocity (V_max) of 164 μg/mL and 0.94 ng/min/μg protein, respectively. At steady state, the intra-cellular/extracellular concentration ratio was 3.4. Naproxen accumulation was more efficient at acidic pH than under neutral or alkaline conditions. Small proportions of glycerol, Pluronic F-127, and glucosylceramide enhanced naproxen entry. The individual and combined effects of glycerol and Pluronic F-127 were of lesser magnitude than those obtained with glucosylceramide or at pH 6.3. Thus, SCC-25 cells possess transporters for naproxen.