Evaluation of HO-1-u-1 cell line as an in vitro model for sublingual drug delivery involving passive diffusion—Initial validation studies

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• 作者：Yanfeng Wang ; Zhong Zuo ; Kenneth K.H. Lee ; Moses S.S. Chow
• 关键词：Sublingual ; HO-1-u-1 ; Permeability ; β ; -Blocker
• 刊名：International Journal of Pharmaceutics
• 出版年：2007
• 出版时间：4 April 2007
• 年：2007
• 卷：334
• 期：1-2
• 页码：27-34
• 全文大小：572 K

文摘

The aim of this study was to provide preliminary validation of a new sublingual mucosal cell line (HO-1-u-1) for use as in vitro sublingual drug delivery screening of compounds involving passive diffusion. HO-1-u-1 cells were seeded on cell culture inserts. The ultrastructure and integrity of cell layers, inter-passage variation and directionality of drug transport, and apparent permeability coefficient (P_app) of eight β-blockers (representing compounds involving passive diffusion) were determined. HO-1-u-1 cells grown on inserts formed stratified and epithelial-like structure and maintained the typical histological features of normal human sublingual epithelium. The maximal integrity of the cell layer was reached in 23 days. No significant inter-passage variation was found at the passages ranging from 2 to 11 when measured by radiolabeled transcellular and paracellular markers (testosterone and mannitol, respectively). Bidirectional transport studies confirmed the passive diffusion as the mechanism of transport for these markers. The P_app of eight β-blockers across HO-1-u-1 cell culture ranged from 2.89 ± 0.17 to 6.37 ± 0.37 × 10⁻⁶ cm/s and correlated well to the P_app obtained from porcine sublingual mucosa (r² = 0.647 and 0.83 when excluding propranolol). The above results indicate that the HO-1-u-1 cells grown on inserts may offer as a potentially in vitro model for screening sublingual drug permeation involving passive diffusion.