Drug Disposition in the Lower Gastrointestinal Tract: Targeting and Monitoring
The increasing prevalence of colonic diseases calls for a better understanding of the various colonic drug absorption barriers of colon-targeted formulations, and for reliable in vitro tools that accurately predict local drug disposition. In vivo relevant incubation conditions have been shown to bet...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-01-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/13/2/161 |
| _version_ | 1797407247559557120 |
|---|---|
| author | Glenn Lemmens Arno Van Camp Stephanie Kourula Tim Vanuytsel Patrick Augustijns |
| author_facet | Glenn Lemmens Arno Van Camp Stephanie Kourula Tim Vanuytsel Patrick Augustijns |
| author_sort | Glenn Lemmens |
| collection | DOAJ |
| description | The increasing prevalence of colonic diseases calls for a better understanding of the various colonic drug absorption barriers of colon-targeted formulations, and for reliable in vitro tools that accurately predict local drug disposition. In vivo relevant incubation conditions have been shown to better capture the composition of the limited colonic fluid and have resulted in relevant degradation and dissolution kinetics of drugs and formulations. Furthermore, drug hurdles such as efflux transporters and metabolising enzymes, and the presence of mucus and microbiome are slowly integrated into drug stability- and permeation assays. Traditionally, the well characterized Caco-2 cell line and the Ussing chamber technique are used to assess the absorption characteristics of small drug molecules. Recently, various stem cell-derived intestinal systems have emerged, closely mimicking epithelial physiology. Models that can assess microbiome-mediated drug metabolism or enable coculturing of gut microbiome with epithelial cells are also increasingly explored. Here we provide a comprehensive overview of the colonic physiology in relation to drug absorption, and review colon-targeting formulation strategies and in vitro tools to characterize colonic drug disposition. |
| first_indexed | 2024-03-09T03:39:00Z |
| format | Article |
| id | doaj.art-fbf599558ae949e7b775962b8cae1475 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T03:39:00Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-fbf599558ae949e7b775962b8cae14752023-12-03T14:44:45ZengMDPI AGPharmaceutics1999-49232021-01-0113216110.3390/pharmaceutics13020161Drug Disposition in the Lower Gastrointestinal Tract: Targeting and MonitoringGlenn Lemmens0Arno Van Camp1Stephanie Kourula2Tim Vanuytsel3Patrick Augustijns4Drug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49—Box 921, 3000 Leuven, BelgiumDrug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49—Box 921, 3000 Leuven, BelgiumDrug Metabolism and Pharmacokinetics, Janssen R&D, Turnhoutseweg 30, 2340 Beerse, BelgiumTranslational Research Center for Gastrointestinal Disorders, TARGID, KU Leuven, Herestraat 49, 3000 Leuven, BelgiumDrug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49—Box 921, 3000 Leuven, BelgiumThe increasing prevalence of colonic diseases calls for a better understanding of the various colonic drug absorption barriers of colon-targeted formulations, and for reliable in vitro tools that accurately predict local drug disposition. In vivo relevant incubation conditions have been shown to better capture the composition of the limited colonic fluid and have resulted in relevant degradation and dissolution kinetics of drugs and formulations. Furthermore, drug hurdles such as efflux transporters and metabolising enzymes, and the presence of mucus and microbiome are slowly integrated into drug stability- and permeation assays. Traditionally, the well characterized Caco-2 cell line and the Ussing chamber technique are used to assess the absorption characteristics of small drug molecules. Recently, various stem cell-derived intestinal systems have emerged, closely mimicking epithelial physiology. Models that can assess microbiome-mediated drug metabolism or enable coculturing of gut microbiome with epithelial cells are also increasingly explored. Here we provide a comprehensive overview of the colonic physiology in relation to drug absorption, and review colon-targeting formulation strategies and in vitro tools to characterize colonic drug disposition.https://www.mdpi.com/1999-4923/13/2/161colonic physiologycolon drug deliverycolonic drug dispositionintestinal in vitro modelsdrug absorptiondrug metabolising enzymes (DME) |
| spellingShingle | Glenn Lemmens Arno Van Camp Stephanie Kourula Tim Vanuytsel Patrick Augustijns Drug Disposition in the Lower Gastrointestinal Tract: Targeting and Monitoring Pharmaceutics colonic physiology colon drug delivery colonic drug disposition intestinal in vitro models drug absorption drug metabolising enzymes (DME) |
| title | Drug Disposition in the Lower Gastrointestinal Tract: Targeting and Monitoring |
| title_full | Drug Disposition in the Lower Gastrointestinal Tract: Targeting and Monitoring |
| title_fullStr | Drug Disposition in the Lower Gastrointestinal Tract: Targeting and Monitoring |
| title_full_unstemmed | Drug Disposition in the Lower Gastrointestinal Tract: Targeting and Monitoring |
| title_short | Drug Disposition in the Lower Gastrointestinal Tract: Targeting and Monitoring |
| title_sort | drug disposition in the lower gastrointestinal tract targeting and monitoring |
| topic | colonic physiology colon drug delivery colonic drug disposition intestinal in vitro models drug absorption drug metabolising enzymes (DME) |
| url | https://www.mdpi.com/1999-4923/13/2/161 |
| work_keys_str_mv | AT glennlemmens drugdispositioninthelowergastrointestinaltracttargetingandmonitoring AT arnovancamp drugdispositioninthelowergastrointestinaltracttargetingandmonitoring AT stephaniekourula drugdispositioninthelowergastrointestinaltracttargetingandmonitoring AT timvanuytsel drugdispositioninthelowergastrointestinaltracttargetingandmonitoring AT patrickaugustijns drugdispositioninthelowergastrointestinaltracttargetingandmonitoring |