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

Abstract:

: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 beta-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 beta-blockers across HO-1-u-1 cell culture ranged from 2.89+/-0.17 to 6.37+/-0.37x10(-6)cm/s and correlated well to the P(app) obtained from porcine sublingual mucosa (r(2)=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.

journal_name

Int J Pharm

authors

Wang Y,Zuo Z,Lee KK,Chow MS

doi

10.1016/j.ijpharm.2006.10.012

subject

Has Abstract

pub_date

2007-04-04 00:00:00

pages

27-34

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(06)00850-7

journal_volume

334

pub_type

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