Immunoliposomes: a new therapeutic option to treat SynGAP1-associated epilepsy
The blood-brain barrier (BBB) hinders the uptake of most drugs into the brain. Thus, active processes, physiologically necessary for nutrient uptake, like receptor-mediated transcytosis have become popular targets for drug transport. One such receptor is the transferrin receptor 1 (TfR), being highl...
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| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
September 2025
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| In: |
European journal of pharmaceutics and biopharmaceutics
Year: 2025, Jahrgang: 214, Pages: 1-11 |
| ISSN: | 1873-3441 |
| DOI: | 10.1016/j.ejpb.2025.114799 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ejpb.2025.114799 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0939641125001766 
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| Verfasserangaben: | K. Wienken, A. Mazur, B. Gericke, S. Petralla, L. Wagner, O. Seifert, R.E. Kontermann, G. Fricker |
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| 245 | 1 | 0 | |a Immunoliposomes |b a new therapeutic option to treat SynGAP1-associated epilepsy |c K. Wienken, A. Mazur, B. Gericke, S. Petralla, L. Wagner, O. Seifert, R.E. Kontermann, G. Fricker |
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| 520 | |a The blood-brain barrier (BBB) hinders the uptake of most drugs into the brain. Thus, active processes, physiologically necessary for nutrient uptake, like receptor-mediated transcytosis have become popular targets for drug transport. One such receptor is the transferrin receptor 1 (TfR), being highly expressed at the BBB. Immunoliposomes targeting the TfR were loaded with rosuvastatin to improve the therapy of SynGAP1-associated epilepsy. The rational of using rosuvastatin is based on its function downregulating the Ras-Raf-MEK-ERK pathway, which is upregulated in excitatory neurons in patients with SynGAP1-related disorders. However, rosuvastatin shows poor BBB permeability. Therefore, immunoliposomes decorated with anti-TfR antibody Ox26 and its single-chain variable fragment (scFv) were prepared and characterized. Immunoliposomes could be prepared reproducibly with a size of about 125 nm, were not hemolytically active and showed colloidal stability in plasma for 2 h. They exhibited a high uptake into endothelial cells which was not altered in presence of the natural ligand transferrin. In vivo application of fluorescently labeled immunoliposomes demonstrated a long plasma half-life and accumulation in brain capillaries. In comparison to unmodified liposomes, Ox26- and scFv-immunoliposomes showed a 2.8- and 2.5-fold improved transfer of rosuvastatin into brain tissue, suggesting successful passage of the BBB. | ||
| 650 | 4 | |a Antibody decoration | |
| 650 | 4 | |a Blood-brain barrier | |
| 650 | 4 | |a Brain-targeting | |
| 650 | 4 | |a Immunoliposomes | |
| 650 | 4 | |a Nanomedicine | |
| 650 | 4 | |a Ox26 antibody | |
| 650 | 4 | |a Rosuvastatin | |
| 650 | 4 | |a SynGAP1 epilepsy | |
| 650 | 4 | |a Transferrin receptor | |
| 700 | 1 | |a Mazur, A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gericke, Birthe |e VerfasserIn |0 (DE-588)132181108X |0 (DE-627)1881697975 |4 aut | |
| 700 | 1 | |a Petralla, Sabrina |e VerfasserIn |0 (DE-588)1262403529 |0 (DE-627)181007066X |4 aut | |
| 700 | 1 | |a Wagner, Lelia |d 1994- |e VerfasserIn |0 (DE-588)1230491139 |0 (DE-627)1752949730 |4 aut | |
| 700 | 1 | |a Seifert, O. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kontermann, R. E. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Fricker, Gert |d 1956- |e VerfasserIn |0 (DE-588)1042227675 |0 (DE-627)768469465 |0 (DE-576)393783464 |4 aut | |
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