Ye, Dongmei, Iris Ma, and Thomas Y. Ma. Molecular mechanism of tumor necrosis factormodulation of intestinal epithelial tight junction barrier. Am J Physiol Gastrointest Liver Physiol 290: G496–G504, 2006; doi:10.1152/ajpgi.00318.2005.—A TNF-induced increase in intestinal epithelial tight junction (TJ) permeability has been proposed to be an important proinflammatory mechanism contributing to i...

Tenofovir disoproxil fumarate (TDF), the bisphosphonate ester prodrug of tenofovir (TFV), has poor bioavailability due to intestinal degradation and efflux transport. Reformulation using U.S. Food and Drug Administration-approved esterase and efflux inhibitors to increase oral bioavailability could provide lower dose alternatives and reduce costs for patients with HIV in resource-limited settin...

The present study explores the potential of nanoemulsion, a lipid drug delivery system, to improve solubility and oral absorption of Silybum marianum extract. The optimized formulation contained 40 mg/mL of commercial extract (4 % w/w) and it was composed of 2.5 g labrasol (20 %) as the oil phase, 1.5 g cremophor EL as the surfactant, and 1 g labrafil as the cosurfactant (mixture surfactant/cos...

Glycosylation of biopharmaceuticals can mediate cell specific delivery by targeting carbohydrate receptors. Additionally, glycosylation can improve the physico-chemical (drug-like) properties of peptide based drug candidates. The main purpose of this study was to examine if glycosylation of the peptide enkephalin could facilitate its binding to the carbohydrate receptor, asialoglycoprotein. Fir...

The permeability estimation from cell monolayer permeation data is usually based on 100% recovery assumption. However, poor recovery is often seen in such experiments in practice but often neglected in data interpretation. In the present study, the cellular retention kinetics during Caco-2 permeation experiments of three passively transported compounds, weakly basic propranolol [(+/-)-1-isoprop...

Intestinal transcellular permeability (P(m)), measured across cell lines such as Caco-2 cells in vitro, is often used for assessing oral drug absorption potential in humans. However, the quantitative link between in vitro permeability and apparent in vivo absorption kinetics, based on drug appearance in plasma, is poorly understood. In the current study, a novel absorption-disposition kinetic m...

A TNF-alpha-induced increase in intestinal epithelial tight junction (TJ) permeability has been proposed to be an important proinflammatory mechanism contributing to intestinal inflammation in Crohn's disease and other inflammatory conditions. Previous studies from our laboratory suggested that the TNF-alpha-induced increase in intestinal TJ permeability was mediated by an increase in myosin li...

In this study, harmine liposomes (HM-lip) were prepared through the thin-film hydration-pH-gradient method and then coated with N-trimethyl chitosan (TMC). Particle size, zeta potential, entrapment efficiency, and in vitro release of HM-lip and TMC-coated harmine liposomes (TMC-HM-lip) were also determined. Sprague Dawley rats were further used to investigate the pharmacokinetics in vivo. Reten...

Caco-2 cells are widely used for both mechanistic studies in molecular cell biology as well as for studies aiming at estimating, in vitro, the bioavailability of drug candidates, xenobiotics, food compounds .... This results largely from the spontaneous differentiation of this human colon adenocarcinoma line into enterocytes-like cells in classical culture conditions, as well as from the use of...