Effects of Absorption Enhancers on the Transport of Model Compounds in Caco-2 Cell Monolayers: Assessment by Confocal Laser Scanning Microscopy

Abstract

Three typical absorption enhancers, i.e., sodium caprate (Cap-Na), sodium deoxycholate (Deo-Na), and dipotassium glycyrrhizinate (Grz-K), were compared in terms of their permeability-enhancing effects on hydrophilic and hydrophobic model compounds in Caco-2 cell monolayers. The transepithelial electrical resistance (TEER) of the monolayers was reduced concentration-dependently by treatment with Cap-Na and Deo-Na, while treatment with Grz-K increased the TEER. Two patterns of TEER reduction were observed: one pattern indicated that Cap-Na had a rapid reducing effect, and another indicated that Deo-Na had a delayed reducing effect. These reductions in the TEER were accompanied by the increased transepithelial transport of two hydrophilic model compounds, sodium fluorescein (Flu-Na; MW = 376, log P = -1.52) and fluorescein isothiocyanate-dextran 4000 (FD-4; MW = 4400, log P = -2.0), and one hydrophobic model compound, rhodamine 123 hydrate (Rh123; MW = 381, log P = 1.13). The transport-enhancing effects of Cap-Na and Deo-Na on these model compounds decreased in the following order: FD-4 > Rh123 > Flu-Na, while Grz-K was found to have no effect on the transport of any of these model compounds. Confocal laser scanning microscopy (CLSM) of Caco-2 cell monolayers revealed that Cap-Na and Deo-Na enhanced the transepithelial transport of the hydrophilic model compounds via the paracellular route and that of the hydrophobic model compound via both paracellular and transcellular routes. Semiquantitative visual information obtained from CLSM images reflected the results of the transport experiment.

Effects of bile salts on the lovastatin pharmacokinetics following oral administration to rats

“…Studies have reported that bile salts enhance the epithelial transport of hydrophilic drugs through the paracellular route and that of hydrophobic compounds through both paracellular and transcellular routes (Sasaki et al, 1997;Shimazaki et al, 1998). Since lovastatin is lipophilic, the enhanced bioavailabilities by the addition of bile salts were thought to be due to the increased transport via both paracellular and transcellular routes.…”

Absorption of sugars in the Egyptian fruit bat (Rousettus aegyptiacus): a paradox explained

“…We highlight Keegan's studies, reported mainly in the form of conference abstracts, to draw attention to a situation in which alternative modes of sugar absorption might be important. In both mammalian and avian species the paracellular route of absorption of water soluble compounds has been visualized using either autoradiography [of radiolabeled polyethylene glycol (Ma et al, 1993)] or confocal laser microscopy [using fluorescein Hurni et al, 1993;Sakai et al, 1997)], its molecular size selectivity has been characterized using a series of nonelectrolyte water-soluble probes that differ in molecular dimension (Chediack et al, 2003;Ghandehari et al, 1997;Hamilton et al, 1987), and its charge selectivity has been characterized using relatively inert, charged peptides (Chediack et al, 2006;He et al, 1998). Our goal was to quantify the level of possible nonmediated absorption.…”

Blood–brain barrier transport studies, aggregation, and molecular dynamics simulation of multiwalled carbon nanotube functionalized with fluorescein isothiocyanate

“…On the contrary, the equilibration point for the FITC-labeled dextran 150 was not reached after 48 hours of incubation ( Figure 2C). The BBB permeation of FITC-dextran system was severely obstructed because of the extensive branching behavior occurring at greater molecular weight (MW 10 kDa) [32][33][34] , high hydrophilic properties (logP =-2.0 for FITC-dextran 4 kDa), 35 and topological polar surface area of dextrans (268.68 Å 2 ). To eliminate the possibility of FITC disintegration from dextran polymer, the FITC molecule was also covalently attached to dextran via random conjugation with any free hydroxyl group at a frequency of 0.003 to 0.02 moles of FITC per mole of glucose.…”