Development and validation of a porcine artificial colonic mucus model reflecting the properties of native colonic mucus in pigs
Colonic mucus plays a key role in colonic drug absorption. Mucus permeation assays could therefore provide useful insights and support rational formulation development in the early stages of drug development. However, the collection of native colonic mucus from animal sources is labor-intensive, doe...
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| Published in | European journal of pharmaceutical sciences Vol. 181; p. 106361 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
01.02.2023
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| Abstract | Colonic mucus plays a key role in colonic drug absorption. Mucus permeation assays could therefore provide useful insights and support rational formulation development in the early stages of drug development. However, the collection of native colonic mucus from animal sources is labor-intensive, does not yield amounts that allow for routine experimentation, and raises ethical concerns. In the present study, we developed an in vitro porcine artificial colonic mucus model based on the characterization of native colonic mucus. The structural properties of the artificial colonic mucus were validated against the native secretion for their ability to capture key diffusion patterns of macromolecules in native mucus. Moreover, the artificial colonic mucus could be stored under common laboratory conditions, without compromising its barrier properties. In conclusion, the porcine artificial colonic mucus model can be considered a biorelevant way to study the diffusion behavior of drug candidates in colonic mucus. It is a cost-efficient screening tool easily incorporated into the early stages of drug development and it contributes to the implementation of the 3Rs (refinement, reduction, and replacement of animals) in the drug development process.
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| AbstractList | Colonic mucus plays a key role in colonic drug absorption. Mucus permeation assays could therefore provide useful insights and support rational formulation development in the early stages of drug development. However, the collection of native colonic mucus from animal sources is labor-intensive, does not yield amounts that allow for routine experimentation, and raises ethical concerns. In the present study, we developed an in vitro porcine artificial colonic mucus model based on the characterization of native colonic mucus. The structural properties of the artificial colonic mucus were validated against the native secretion for their ability to capture key diffusion patterns of macromolecules in native mucus. Moreover, the artificial colonic mucus could be stored under common laboratory conditions, without compromising its barrier properties. In conclusion, the porcine artificial colonic mucus model can be considered a biorelevant way to study the diffusion behavior of drug candidates in colonic mucus. It is a cost-efficient screening tool easily incorporated into the early stages of drug development and it contributes to the implementation of the 3Rs (refinement, reduction, and replacement of animals) in the drug development process.
[Display omitted] Colonic mucus plays a key role in colonic drug absorption. Mucus permeation assays could therefore provide useful insights and support rational formulation development in the early stages of drug development. However, the collection of native colonic mucus from animal sources is labor-intensive, does not yield amounts that allow for routine experimentation, and raises ethical concerns. In the present study, we developed an in vitro porcine artificial colonic mucus model based on the characterization of native colonic mucus. The structural properties of the artificial colonic mucus were validated against the native secretion for their ability to capture key diffusion patterns of macromolecules in native mucus. Moreover, the artificial colonic mucus could be stored under common laboratory conditions, without compromising its barrier properties. In conclusion, the porcine artificial colonic mucus model can be considered a biorelevant way to study the diffusion behavior of drug candidates in colonic mucus. It is a cost-efficient screening tool easily incorporated into the early stages of drug development and it contributes to the implementation of the 3Rs (refinement, reduction, and replacement of animals) in the drug development process. |
| ArticleNumber | 106361 |
| Author | Karlsson, Eva Marie-Louise Pedersen, Betty Lomstein Barmpatsalou, Vicky Jacobson, Magdalena Rodler, Agnes Bergström, Christel Anna Sofie |
| Author_xml | – sequence: 1 givenname: Vicky surname: Barmpatsalou fullname: Barmpatsalou, Vicky organization: The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, Box 580, SE-751 23, Uppsala, Sweden – sequence: 2 givenname: Agnes surname: Rodler fullname: Rodler, Agnes organization: The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, Box 580, SE-751 23, Uppsala, Sweden – sequence: 3 givenname: Magdalena surname: Jacobson fullname: Jacobson, Magdalena organization: Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Sciences, Swedish University of Agricultural Sciences, Box 7054, SE-750 07, Uppsala, Sweden – sequence: 4 givenname: Eva Marie-Louise surname: Karlsson fullname: Karlsson, Eva Marie-Louise organization: Oral Product Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Gothenburg, Sweden – sequence: 5 givenname: Betty Lomstein surname: Pedersen fullname: Pedersen, Betty Lomstein organization: Product Development & Drug Delivery, Global Pharmaceutical R&D, Ferring Pharmaceuticals A/S, Amager Strandvej 405, Kastrup 2770, Denmark – sequence: 6 givenname: Christel Anna Sofie orcidid: 0000-0002-8917-2612 surname: Bergström fullname: Bergström, Christel Anna Sofie email: christel.bergstrom@farmaci.uu.se organization: The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, Box 580, SE-751 23, Uppsala, Sweden |
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