دورية أكاديمية
Local delivery of liposomal prednisolone leads to an anti-inflammatory profile in renal ischaemia-reperfusion injury in the rat.
| العنوان: | Local delivery of liposomal prednisolone leads to an anti-inflammatory profile in renal ischaemia-reperfusion injury in the rat. |
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| المؤلفون: | van Alem CMA; Department of Internal Medicine - Nephrology, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands., Boonstra M; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands., Prins J; Department of Internal Medicine - Nephrology, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands., Bezhaeva T; Department of Internal Medicine - Nephrology, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands., van Essen MF; Department of Internal Medicine - Nephrology, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands., Ruben JM; Department of Internal Medicine - Nephrology, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands., Vahrmeijer AL; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands., van der Veer EP; Department of Internal Medicine - Nephrology, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands., de Fijter JW; Department of Internal Medicine - Nephrology, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands., Reinders ME; Department of Internal Medicine - Nephrology, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands., Meijer O; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.; Department of Internal Medicine - Endocrinology, Leiden University Medical Center, Leiden, The Netherlands., Metselaar JM; Management team, Enceladus Pharmaceuticals, Naarden, The Netherlands.; Department of Experimental Molecular Imaging, University Clinic, RWTH Aachen University, Aachen, Germany., van Kooten C; Department of Internal Medicine - Nephrology, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands., Rotmans JI; Department of Internal Medicine - Nephrology, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands. |
| المصدر: | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association [Nephrol Dial Transplant] 2018 Jan 01; Vol. 33 (1), pp. 44-53. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 8706402 Publication Model: Print Cited Medium: Internet ISSN: 1460-2385 (Electronic) Linking ISSN: 09310509 NLM ISO Abbreviation: Nephrol Dial Transplant Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Oxford University Press Original Publication: [Berlin ; New York, NY] : Springer International, [c1986- |
| مواضيع طبية MeSH: | Drug Delivery Systems*, Anti-Inflammatory Agents/*therapeutic use , Inflammation/*prevention & control , Inflammation Mediators/*metabolism , Liposomes/*administration & dosage , Prednisolone/*therapeutic use , Reperfusion Injury/*drug therapy, Animals ; Cells, Cultured ; Humans ; Inflammation/metabolism ; Liposomes/chemistry ; Macrophages/cytology ; Macrophages/drug effects ; Male ; Rats ; Rats, Inbred Lew ; Reperfusion Injury/metabolism |
| مستخلص: | Background: Treatment of inflammatory kidney diseases with systemic high-dose glucocorticoids (GCs) has severe side effects. Liposomal encapsulation could facilitate local delivery of GCs to the inflamed kidney, as liposomes encapsulate their payload until extravasation at sites of inflammation, potentially resulting in local bioactivity. Our aim was to evaluate the ability of liposomes to accumulate locally after renal ischaemia-reperfusion injury in the rat and to study its effect on macrophages. Methods: In vitro, human macrophages were incubated with fluorescent liposomes, liposomal prednisolone, prednisolone, empty liposomes or saline. Uptake was studied microscopically and treatment effect was assessed by interkeukin 6 (IL-6) enzyme-linked immunosorbent assay. The mechanism of action was evaluated by analysing GC receptor activation by microscopy and quantitative polymerase chain reaction (qPCR). In vivo, rats were subjected to ischaemia-reperfusion injury and were injected intravenously with fluorescent liposomes, liposomal prednisolone, prednisolone, empty liposomes or saline. Uptake was measured by the FLARE camera and the treatment effect by immunohistochemistry for myeloid cells and qPCR for inflammatory markers. Results: In vitro, macrophages internalized liposomes after 8 hours. Prednisolone or liposomal prednisolone treatment reduced IL-6 production and both compounds induced translocation of the GC receptor to the nucleus and upregulation of PER1 messenger RNA (mRNA), indicating a similar mechanism of action. In vivo, fluorescent liposomes accumulated in the inflamed kidney. Liposomal prednisolone treatment increased the presence of ED2-positive anti-inflammatory macrophages and both prednisolone and liposomal prednisolone reduced monocyte chemoattractant protein-1 (MCP-1) mRNA production, indicating a reduced pro-inflammatory profile in the kidney. Conclusions: Liposomal encapsulation is a promising strategy for local delivery of glucocorticoids to the inflamed kidney. (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.) |
| فهرسة مساهمة: | Keywords: acute kidney injury; inflammatory kidney disease; liposomal prednisolone; local delivery; macrophage |
| المشرفين على المادة: | 0 (Anti-Inflammatory Agents) 0 (Inflammation Mediators) 0 (Liposomes) 9PHQ9Y1OLM (Prednisolone) |
| تواريخ الأحداث: | Date Created: 20171010 Date Completed: 20181127 Latest Revision: 20220316 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1093/ndt/gfx204 |
| PMID: | 28992069 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1460-2385 |
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| DOI: | 10.1093/ndt/gfx204 |