Publikationer från Malmö universitet
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  • 1.
    Riaz, Azra
    et al.
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Gidvall, Sanna
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Prgomet, Zdenka
    Malmö universitet, Odontologiska fakulteten (OD).
    Hernandez, Aura Rocio
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Ruzgas, Tautgirdas
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Nilsson, Emelie J.
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Davies, Julia R
    Malmö universitet, Odontologiska fakulteten (OD). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Valetti, Sabrina
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Three-Dimensional Oral Mucosal Equivalents as Models for Transmucosal Drug Permeation Studies2023Inngår i: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 15, nr 5, s. 1513-1513Artikkel i tidsskrift (Fagfellevurdert)
    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.).

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  • 2.
    Valetti, Sabrina
    et al.
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Riaz, Azra
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Doko, Anemona
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Sultana, Kaiser
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Eskandari, Mahboubeh
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Prgomet, Zdenka
    Malmö universitet, Odontologiska fakulteten (OD).
    Feiler, Adam
    Nanologica AB, 151 36 Södertälje, Sweden; Chemistry Department, KTH, Royal Institute of Technology, 100 44 Stockholm, Sweden.
    Rönn, Robert
    Orexo AB, 754 50 Uppsala, Sweden.
    Dahlström, Bengt
    CTC Clinical Trial Consultants AB, 75237 Uppsala, Sweden.
    Engblom, Johan
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Björklund, Sebastian
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Oral transmucosal delivery of eletriptan for neurological diseases.2022Inngår i: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 627, artikkel-id 122222Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Migraine is a highly prevalent neurological disease affecting circa 1 billion patients worldwide with severe incapacitating symptoms, which significantly diminishes the quality of life. As self-medication practice, oral administration of triptans is the most common option, despite its relatively slow therapeutic onset and low drug bioavailability. To overcome these issues, here we present, to the best of our knowledge, the first study on the possibility of oral transmucosal delivery of one of the safest triptans, namely eletriptan hydrobromide (EB). Based on a comprehensive set of in vitro and ex vivo experiments, we highlight the conditions required for oral transmucosal delivery, potentially giving rise to similar, or even higher, drug plasma concentrations expected from conventional oral administration. With histology and tissue integrity studies, we conclude that EB neither induces morphological changes nor impairs the integrity of the mucosal barrier following 4 h of exposure. On a cellular level, EB is internalized in human oral keratinocytes within the first 5 min without inducing toxicity at the relevant concentrations for transmucosal delivery. Considering that the pKa of EB falls within the physiologically range, we systematically investigated the effect of pH on both solubility and transmucosal permeation. When the pH is increased from 6.8 to 10.4, the drug solubility decreases drastically from 14.7 to 0.07 mg/mL. At pH 6.8, EB gave rise to the highest drug flux and total permeated amount across mucosa, while at pH 10.4 EB shows greater permeability coefficient and thus higher ratio of permeated drug versus applied drug. Permeation experiments with model membranes confirmed the pH dependent permeation profile of EB. The distribution of EB in different cellular compartments of keratinocytes is pH dependent. In brief, high drug ionization leads to higher association with the cell membrane, suggesting ionic interactions between EB and the phospholipid head groups. Moreover, we show that the chemical permeation enhancer DMSO can be used to enhance the drug permeation significantly (i.e., 12 to 36-fold increase). Taken together, this study presents important findings on transmucosal delivery of eletriptan via the oral cavity and paves the way for clinical investigations for a fast and safe migraine treatment.

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