Development of a canine artificial colonic mucus model for drug diffusion studies.

Autor: Barmpatsalou V; The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, Box 580, SE-751 23, Uppsala, Sweden., Tjakra M; The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, Box 580, SE-751 23, Uppsala, Sweden., Li L; The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, Box 580, SE-751 23, Uppsala, Sweden., Dubbelboer IR; The Swedish Drug Delivery Center, Department of Pharmaceutical Biosciences, Uppsala University, Box 574, SE-751 23, Uppsala, Sweden., Karlsson E; Oral Product Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Gothenburg, Sweden., Pedersen Lomstein B; Product Development & Drug Delivery, Global Pharmaceutical R&D, Ferring Pharmaceuticals A/S, Amager Strandvej 405, 2770, Kastrup, Denmark., Bergström CAS; The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, Box 580, SE-751 23, Uppsala, Sweden. Electronic address: christel.bergstrom@farmaci.uu.se.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2024 Mar 01; Vol. 194, pp. 106702. Date of Electronic Publication: 2024 Jan 12.
DOI: 10.1016/j.ejps.2024.106702
Abstrakt: Colonic mucus is a key factor in the colonic environment because it may affect drug absorption. Due to the similarity of human and canine gastrointestinal physiology, dogs are an established preclinical species for the assessment of controlled release formulations. Here we report the development of an artificial colonic mucus model to mimic the native canine one. In vitro models of the canine colonic environment can provide insights for early stages of drug development and contribute to the implementation of the 3Rs (refinement, reduction, and replacement) of animal usage in the drug development process. Our artificial colonic mucus could predict diffusion trends observed in native mucus and was successfully implemented in microscopic and macroscopic assays to study macromolecular permeation through the mucus. The traditional Transwell set up was optimized with the addition of a nylon filter to ensure homogenous representation of the mucus barrier in vitro. In conclusion, the canine artificial colonic mucus can be used to study drug permeation across the mucus and its flexibility allows its use in various set ups depending on the nature of the compound under investigation and equipment availability.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: