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Tailoring the Lamellarity of Liposomes Prepared by Dual Centrifugation

Dual centrifugation (DC) is a new and versatile technique for the preparation of liposomes by in-vial homogenization of lipid-water mixtures. Size, size distribution, and entrapping efficiencies are strongly dependent on the lipid concentration during DC-homogenization. In this study, we investigate...

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Autores principales: Koehler, Jonas K., Gedda, Lars, Wurster, Leonie, Schnur, Johannes, Edwards, Katarina, Heerklotz, Heiko, Massing, Ulrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961234/
https://www.ncbi.nlm.nih.gov/pubmed/36840028
http://dx.doi.org/10.3390/pharmaceutics15020706
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author Koehler, Jonas K.
Gedda, Lars
Wurster, Leonie
Schnur, Johannes
Edwards, Katarina
Heerklotz, Heiko
Massing, Ulrich
author_facet Koehler, Jonas K.
Gedda, Lars
Wurster, Leonie
Schnur, Johannes
Edwards, Katarina
Heerklotz, Heiko
Massing, Ulrich
author_sort Koehler, Jonas K.
collection PubMed
description Dual centrifugation (DC) is a new and versatile technique for the preparation of liposomes by in-vial homogenization of lipid-water mixtures. Size, size distribution, and entrapping efficiencies are strongly dependent on the lipid concentration during DC-homogenization. In this study, we investigated the detailed structure of DC-made liposomes. To do so, an assay to determine the ratio of inner to total membrane surfaces of liposomes (inaccessible surface) was developed based on either time-resolved or steady-state fluorescence spectroscopy. In addition, cryogenic electron microscopy (cryo-EM) was used to confirm the lamellarity results and learn more about liposome morphology. One striking result leads to the possibility of producing a novel type of liposome—small multilamellar vesicles (SMVs) with low PDI, sizes of the order of 100 nm, and almost completely filled with bilayers. A second particularly important finding is that VPGs can be prepared to contain open bilayer structures that will close spontaneously when, after storage, more aqueous phase is added and liposomes are formed. Through this process, a drug can effectively be entrapped immediately before application. In addition, dual centrifugation at lower lipid concentrations is found to produce predominantly unilamellar vesicles.
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spelling pubmed-99612342023-02-26 Tailoring the Lamellarity of Liposomes Prepared by Dual Centrifugation Koehler, Jonas K. Gedda, Lars Wurster, Leonie Schnur, Johannes Edwards, Katarina Heerklotz, Heiko Massing, Ulrich Pharmaceutics Article Dual centrifugation (DC) is a new and versatile technique for the preparation of liposomes by in-vial homogenization of lipid-water mixtures. Size, size distribution, and entrapping efficiencies are strongly dependent on the lipid concentration during DC-homogenization. In this study, we investigated the detailed structure of DC-made liposomes. To do so, an assay to determine the ratio of inner to total membrane surfaces of liposomes (inaccessible surface) was developed based on either time-resolved or steady-state fluorescence spectroscopy. In addition, cryogenic electron microscopy (cryo-EM) was used to confirm the lamellarity results and learn more about liposome morphology. One striking result leads to the possibility of producing a novel type of liposome—small multilamellar vesicles (SMVs) with low PDI, sizes of the order of 100 nm, and almost completely filled with bilayers. A second particularly important finding is that VPGs can be prepared to contain open bilayer structures that will close spontaneously when, after storage, more aqueous phase is added and liposomes are formed. Through this process, a drug can effectively be entrapped immediately before application. In addition, dual centrifugation at lower lipid concentrations is found to produce predominantly unilamellar vesicles. MDPI 2023-02-20 /pmc/articles/PMC9961234/ /pubmed/36840028 http://dx.doi.org/10.3390/pharmaceutics15020706 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Koehler, Jonas K.
Gedda, Lars
Wurster, Leonie
Schnur, Johannes
Edwards, Katarina
Heerklotz, Heiko
Massing, Ulrich
Tailoring the Lamellarity of Liposomes Prepared by Dual Centrifugation
title Tailoring the Lamellarity of Liposomes Prepared by Dual Centrifugation
title_full Tailoring the Lamellarity of Liposomes Prepared by Dual Centrifugation
title_fullStr Tailoring the Lamellarity of Liposomes Prepared by Dual Centrifugation
title_full_unstemmed Tailoring the Lamellarity of Liposomes Prepared by Dual Centrifugation
title_short Tailoring the Lamellarity of Liposomes Prepared by Dual Centrifugation
title_sort tailoring the lamellarity of liposomes prepared by dual centrifugation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961234/
https://www.ncbi.nlm.nih.gov/pubmed/36840028
http://dx.doi.org/10.3390/pharmaceutics15020706
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