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Investigation of Cellular Interactions of Lipid-Structured Nanoparticles With Oral Mucosal Epithelial Cells

Lipid-based nanosystems enable intracellular delivery of drugs in the oral cavity for the treatment of local diseases. To rationally design such systems, suitable matrix compositions and particle properties need to be identified, and manufacturing technologies that allow reproducible production have...

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Autores principales: Jeitler, R., Glader, C., Tetyczka, C., Zeiringer, S., Absenger-Novak, M., Selmani, A., Fröhlich, E., Roblegg, E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170126/
https://www.ncbi.nlm.nih.gov/pubmed/35677878
http://dx.doi.org/10.3389/fmolb.2022.917921
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author Jeitler, R.
Glader, C.
Tetyczka, C.
Zeiringer, S.
Absenger-Novak, M.
Selmani, A.
Fröhlich, E.
Roblegg, E.
author_facet Jeitler, R.
Glader, C.
Tetyczka, C.
Zeiringer, S.
Absenger-Novak, M.
Selmani, A.
Fröhlich, E.
Roblegg, E.
author_sort Jeitler, R.
collection PubMed
description Lipid-based nanosystems enable intracellular delivery of drugs in the oral cavity for the treatment of local diseases. To rationally design such systems, suitable matrix compositions and particle properties need to be identified, and manufacturing technologies that allow reproducible production have to be applied. This is a prerequisite for the reliable and predictable performance of in-vitro biological studies. Here, we showed that solid lipid nanoparticles (SLN, palmitic acid) and nanostructured lipid carriers (NLC, palmitic acid and oleic acid in different ratios) with a size of 250 nm, a negative zeta potential, and a polydispersity index (PdI) of less than 0.3 can be reproducibly prepared by high-pressure homogenization using quality by design and a predictive model. SLN and NLC were colloidally stable after contact with physiological fluid and did not form agglomerates. The in-vitro studies clearly showed that besides particle size, surface charge and hydrophobicity, matrix composition had a significant effect. More specifically, the addition of the liquid lipid oleic acid increased the cellular uptake capacity without changing the underlying uptake mechanism. Regardless of the matrix composition, caveolin-mediated endocytosis was the major route of uptake, which was confirmed by particle localization in the endoplasmic reticulum. Thus, this work provides useful insights into the optimal composition of lipid carrier systems to enhance the intracellular uptake capacity of drugs into the oral mucosa.
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spelling pubmed-91701262022-06-07 Investigation of Cellular Interactions of Lipid-Structured Nanoparticles With Oral Mucosal Epithelial Cells Jeitler, R. Glader, C. Tetyczka, C. Zeiringer, S. Absenger-Novak, M. Selmani, A. Fröhlich, E. Roblegg, E. Front Mol Biosci Molecular Biosciences Lipid-based nanosystems enable intracellular delivery of drugs in the oral cavity for the treatment of local diseases. To rationally design such systems, suitable matrix compositions and particle properties need to be identified, and manufacturing technologies that allow reproducible production have to be applied. This is a prerequisite for the reliable and predictable performance of in-vitro biological studies. Here, we showed that solid lipid nanoparticles (SLN, palmitic acid) and nanostructured lipid carriers (NLC, palmitic acid and oleic acid in different ratios) with a size of 250 nm, a negative zeta potential, and a polydispersity index (PdI) of less than 0.3 can be reproducibly prepared by high-pressure homogenization using quality by design and a predictive model. SLN and NLC were colloidally stable after contact with physiological fluid and did not form agglomerates. The in-vitro studies clearly showed that besides particle size, surface charge and hydrophobicity, matrix composition had a significant effect. More specifically, the addition of the liquid lipid oleic acid increased the cellular uptake capacity without changing the underlying uptake mechanism. Regardless of the matrix composition, caveolin-mediated endocytosis was the major route of uptake, which was confirmed by particle localization in the endoplasmic reticulum. Thus, this work provides useful insights into the optimal composition of lipid carrier systems to enhance the intracellular uptake capacity of drugs into the oral mucosa. Frontiers Media S.A. 2022-05-23 /pmc/articles/PMC9170126/ /pubmed/35677878 http://dx.doi.org/10.3389/fmolb.2022.917921 Text en Copyright © 2022 Jeitler, Glader, Tetyczka, Zeiringer, Absenger-Novak, Selmani, Fröhlich and Roblegg. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Jeitler, R.
Glader, C.
Tetyczka, C.
Zeiringer, S.
Absenger-Novak, M.
Selmani, A.
Fröhlich, E.
Roblegg, E.
Investigation of Cellular Interactions of Lipid-Structured Nanoparticles With Oral Mucosal Epithelial Cells
title Investigation of Cellular Interactions of Lipid-Structured Nanoparticles With Oral Mucosal Epithelial Cells
title_full Investigation of Cellular Interactions of Lipid-Structured Nanoparticles With Oral Mucosal Epithelial Cells
title_fullStr Investigation of Cellular Interactions of Lipid-Structured Nanoparticles With Oral Mucosal Epithelial Cells
title_full_unstemmed Investigation of Cellular Interactions of Lipid-Structured Nanoparticles With Oral Mucosal Epithelial Cells
title_short Investigation of Cellular Interactions of Lipid-Structured Nanoparticles With Oral Mucosal Epithelial Cells
title_sort investigation of cellular interactions of lipid-structured nanoparticles with oral mucosal epithelial cells
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170126/
https://www.ncbi.nlm.nih.gov/pubmed/35677878
http://dx.doi.org/10.3389/fmolb.2022.917921
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