Regional permeability of salmon calcitonin in isolated rat gastrointestinal tracts: Transport mechanism using Caco-2 cell monolayer
Journal Title: The AAPS Journal - Year 2004, Vol 6, Issue 4
Abstract
The objective of the study was to determine the region of maximum permeation of salmon calcitonin (sCT) through the gastrointestinal tract and to investigate the mechanism of permeation. For regional permeability determination, male Sprague-Dawley rats (250–300 g) were anesthetized and the gastrointestinal tissues were isolated. Stomach, duodenum, jejunum, ileum, or colon tissues were mounted on Navicyte side-by-side diffusion apparatus. Salmon calcitonin solutions (50 μM in phosphate-buffered saline, pH 7.4, 37°C) were added to the donor side, and the samples were removed from the receiver compartment and analyzed by competitive radioimmunoassay (RIA). For mechanistic studies, Caco-2 cells were grown on Transwell inserts (0.4-μm pore size, 0.33 cm2 area) in a humidified 37°C incubator (with 5% CO2). Transport experiments were conducted for sCT solutions (50 μM in Dulbecco's modified eagle's medium [DMEM], pH 7.4) from the apical-to-basolateral (A-to-B) direction and B-to-A direction at 37°C and from the A-to-B direction at 4°C. Cell monolayer integrity was monitored by mannitol permeability and transepithelial electrical resistance (TEER) measurements. The permeability coefficients (× 10−9, cm/sec) for sCT through rat stomach, duodenum, jejunum, ileum, and colon tissues were 0.482±0.086, 0.718±0.025, 0.830±0.053, 1.537±0.32, and 0.934±0.15, respectively. The region of maximum sCT permeability is ileum followed by colon, jejunum, duodenum, and stomach. The permeability coefficients (× 10−6, cm/sec) for sCT through Caco-2 cell monolayer were 8.57±2.34 (A-to-B, 37°C), 8.01±1.22 (A-to-B, 4°C), and 6.15±1.97 (B-to-A, 37°C). The mechanism of its permeation is passive diffusion through the mucosa as determined from the Caco-2 monolayer permeability of sCT.
Authors and Affiliations
Rakhi B. Shah, Mansoor A. Khan
Keywords
Related Articles
- EP ID EP681937
- DOI 10.1208/aapsj060431
- Views 69
- Downloads 0
A Priori Identifiability of Target-Mediated Drug Disposition Models and Approximations
The online version of this article (doi:10.1208/s12248-015-9795-8) contains supplementary material, which is available to authorized users.
Enhancement of MHC-I Antigen Presentation via Architectural Control of pH-Responsive, Endosomolytic Polymer Nanoparticles
The online version of this article (doi:10.1208/s12248-014-9697-1) contains supplementary material, which is available to authorized users.
Development and Fit-for-Purpose Validation of a Soluble Human Programmed Death-1 Protein Assay
The online version of this article (doi:10.1208/s12248-015-9762-4) contains supplementary material, which is available to authorized users.
Procedural elements involved in maintaining bioanalytical data integrity for good laboratory practices studies and regulated clinical studies
This article describes procedural elements involved in ensuring the integrity of bioanalytical data. These elements can be divided into 3 areas. First, there are those ensuring the integrity of the analyte until analysis...
Pre-Existing Biotherapeutic-Reactive Antibodies: Survey Results Within the American Association of Pharmaceutical Scientists
The immunogenicity profile of a biotherapeutic is determined by a multitude of product and patient-related risk factors that can influence the observed incidence and clinical consequences of immunogenicity. Pre-existing...