Academic Journal
Lipid excipients as key modulators of the apparent intestinal permeability in lipid-based formulations: Insights from Caco-2 and Caco-2/HT29-MTX models.
| Τίτλος: | Lipid excipients as key modulators of the apparent intestinal permeability in lipid-based formulations: Insights from Caco-2 and Caco-2/HT29-MTX models. |
|---|---|
| Συγγραφείς: | Bourderi-Cambon A; Université Clermont Auvergne, INRAE, UMR 0454 MEDIS, F-63000 Clermont-Ferrand, France; Gattefossé SAS, 36 Chemin de Genas, 69804 Saint-Priest, France., Fadhlaoui K; Université Clermont Auvergne, INRAE, UMR 0454 MEDIS, F-63000 Clermont-Ferrand, France; Université Clermont Auvergne, CNRS, UMR 6023 LMGE, F-63000 Clermont-Ferrand, France., Garrait G; Université Clermont Auvergne, INRAE, UMR 0454 MEDIS, F-63000 Clermont-Ferrand, France., Rossano M; Gattefossé SAS, 36 Chemin de Genas, 69804 Saint-Priest, France., Miolane C; Gattefossé SAS, 36 Chemin de Genas, 69804 Saint-Priest, France., Caisse P; Gattefossé SAS, 36 Chemin de Genas, 69804 Saint-Priest, France., Beyssac E; Université Clermont Auvergne, INRAE, UMR 0454 MEDIS, F-63000 Clermont-Ferrand, France. Electronic address: eric.beyssac@uca.fr. |
| Πηγή: | European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2026 Jun; Vol. 223, pp. 115055. Date of Electronic Publication: 2026 Mar 14. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 9109778 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3441 (Electronic) Linking ISSN: 09396411 NLM ISO Abbreviation: Eur J Pharm Biopharm Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier Science Original Publication: Stuttgart : Wissenschaftliche Verlagsgesellschaft, c1991- |
| Ιατρικοί όροι (MeSH): | Lipids*/chemistry , Excipients*/chemistry , Intestinal Absorption*/drug effects , Intestinal Absorption*/physiology , Intestinal Mucosa*/metabolism, Permeability/drug effects ; Chemistry, Pharmaceutical/methods ; Drug Compounding/methods ; Humans ; Caco-2 Cells ; HT29 Cells ; Coculture Techniques ; Solubility ; Intestinal Barrier Function |
| Περίληψη: | Lipid-based formulations (LBFs) represent a promising strategy to improve the oral absorption of poorly soluble and poorly permeable compounds, such as BCS Class IV drug. Nevertheless, the development of lipid formulations requires predictive in vitro models that closely mimic in vivo physiology, allowing for more reliable estimation of oral absorption. Permeability studies using culture cells monolayers can contribute to evaluate the influence of formulation components as well as the interplay between solubilisation and permeation. In this study, the cytotoxicity of ticagrelor, a BCS class IV drug, and placebo formulations was first assessed in Caco-2 cells, and selected LBFs were subsequently validated in both Caco-2 monoculture and Caco-2/HT29-MTX co-culture. The apparent permeability (Papp) was estimated using the well-established Caco-2 monoculture model and the more innovative Caco-2/HT29-MTX co-culture, which incorporates mucus secretion to better mimic the intestinal barrier. LC/MS analysis from permeability studies revealed that the apparent permeability coefficient of the pure API (1.02 × 10-7 cm/s for monoculture and 1.25 × 10-7 cm/s for co-culture) was significantly enhanced, by a factor ranging from 4.6 to 9.4 for monoculture, and from 2.1 to 6.6 for co-culture, when formulated in LBFs. The inclusion of permeation enhancers in the LBFs increased Papp values compared for LBFs without permeation enhancers. Overall, a decrease in permeability was observed in the co-culture model due to the mucus barrier, although this reduction was not statistically significant for the majority of tested formulations. (Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Apparent permeability; Caco-2; Co-culture; HT29-MTX; Lipid excipients; Lipid-based formulations; Permeation enhancers |
| Substance Nomenclature: | 0 (Lipids) 0 (Excipients) |
| Entry Date(s): | Date Created: 20260316 Date Completed: 20260711 Latest Revision: 20260711 |
| Update Code: | 20260711 |
| DOI: | 10.1016/j.ejpb.2026.115055 |
| PMID: | 41833799 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1873-3441 |
|---|---|
| DOI: | 10.1016/j.ejpb.2026.115055 |