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Three-Dimensional Oral Mucosal Equivalents as Models for Transmucosal Drug Permeation Studies
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
Malmö University, Faculty of Odontology (OD).
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.ORCID iD: 0000-0003-1383-754X
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2023 (English)In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 15, no 5, p. 1513-1513Article in journal (Refereed) Published
Abstract [en]

Oral transmucosal administration, where drugs are absorbed directly through the non-keratinized, lining mucosa of the mouth, represents a solution to drug delivery with several advantages. Oral mucosal equivalents (OME) developed as 3D in vitro models are of great interest since they express the correct cell differentiation and tissue architecture, simulating the in vivo conditions better than monolayer cultures or animal tissues. The aim of this work was to develop OME to be used as a membrane for drug permeation studies. We developed both full-thickness (i.e., connective plus epithelial tissue) and split-thickness (i.e., only epithelial tissue) OME using non-tumor-derived human keratinocytes OKF6 TERT-2 obtained from the floor of the mouth. All the OME developed here presented similar transepithelial electrical resistance (TEER) values, comparable to the commercial EpiOral™. Using eletriptan hydrobromide as a model drug, we found that the full-thickness OME had similar drug flux to EpiOral™ (28.8 vs. 29.6 µg/cm2/h), suggesting that the model had the same permeation barrier properties. Furthermore, full-thickness OME showed an increase in ceramide content together with a decrease in phospholipids in comparison to the monolayer culture, indicating that lipid differentiation occurred due to the tissue-engineering protocols. The split-thickness mucosal model resulted in 4–5 cell layers with basal cells still undergoing mitosis. The optimum period at the air–liquid interface for this model was twenty-one days; after longer times, signs of apoptosis appeared. Following the 3R principles, we found that the addition of Ca2+, retinoic acid, linoleic acid, epidermal growth factor and bovine pituitary extract was important but not sufficient to fully replace the fetal bovine serum. Finally, the OME models presented here offer a longer shelf-life than the pre-existing models, which paves the way for the further investigation of broader pharmaceutical applications (i.e., long-term drug exposure, effect on the keratinocytes’ differentiation and inflammatory conditions, etc.).

Place, publisher, year, edition, pages
MDPI, 2023. Vol. 15, no 5, p. 1513-1513
Keywords [en]
oral transmucosal delivery, oral mucosal equivalents, drug permeation, 3R principles, 3D in vitro models
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:mau:diva-61046DOI: 10.3390/pharmaceutics15051513ISI: 000997495400001PubMedID: 37242755Scopus ID: 2-s2.0-85160448981OAI: oai:DiVA.org:mau-61046DiVA, id: diva2:1770819
Funder
The Crafoord Foundation, 20210937Knowledge Foundation, 20190010Available from: 2023-06-19 Created: 2023-06-19 Last updated: 2023-08-15Bibliographically approved

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Riaz, AzraGidvall, SannaPrgomet, ZdenkaRuzgas, TautgirdasNilsson, Emelie J.Davies, Julia RValetti, Sabrina

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Riaz, AzraGidvall, SannaPrgomet, ZdenkaHernandez, Aura RocioRuzgas, TautgirdasNilsson, Emelie J.Davies, Julia RValetti, Sabrina
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Department of Biomedical Science (BMV)Biofilms Research Center for BiointerfacesFaculty of Odontology (OD)
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