RGD-coated polymeric microbubbles promote ultrasound-mediated drug delivery in an inflamed endothelium-pericyte co-culture model of the blood-brain barrier
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| Názov: | RGD-coated polymeric microbubbles promote ultrasound-mediated drug delivery in an inflamed endothelium-pericyte co-culture model of the blood-brain barrier |
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| Autori: | Christopher Hark, Junlin Chen, Julia Blöck, Eva Miriam Buhl, Harald Radermacher, Robert Pola, Michal Pechar, Tomáš Etrych, Quim Peña, Anne Rix, Natascha I. Drude, Fabian Kiessling, Twan Lammers, Jan-Niklas May |
| Zdroj: | Drug Deliv Transl Res Drug Delivery and Translational Research |
| Informácie o vydavateľovi: | Springer Science and Business Media LLC, 2024. |
| Rok vydania: | 2024 |
| Predmety: | Inflammation, 0301 basic medicine, 0303 health sciences, Microbubbles, Polymers, Endothelial Cells, Antiviral Agents, Microbubbles [MeSH], Polymers/administration, Antiviral Agents/pharmacokinetics [MeSH], Drug delivery, Endothelial Cells/drug effects [MeSH], Ribavirin/pharmacokinetics [MeSH], Pericytes/drug effects [MeSH], Oligopeptides/chemistry [MeSH], Original Article, Blood-Brain Barrier/metabolism [MeSH], Ribavirin/administration, Inflammation/drug therapy [MeSH], Polymers/chemistry [MeSH], Coculture Techniques [MeSH], Ultrasonic Waves [MeSH], Drug Delivery Systems/methods [MeSH], Sonopermeation, Endothelial Cells/metabolism [MeSH], Humans [MeSH], Antiviral Agents/pharmacology [MeSH], Ribavirin/chemistry [MeSH], Ultrasound, Blood-brain barrier, Pericytes/metabolism [MeSH], Oligopeptides/pharmacokinetics [MeSH], Antiviral Agents/chemistry [MeSH], Antiviral Agents/administration, Oligopeptides/administration, Coculture Techniques, 03 medical and health sciences, Drug Delivery Systems, Ultrasonic Waves, Blood-Brain Barrier, Ribavirin, Humans, Pericytes, Oligopeptides |
| Popis: | Drug delivery to central nervous pathologies is compromised by the blood-brain barrier (BBB). A clinically explored strategy to promote drug delivery across the BBB is sonopermeation, which relies on the combined use of ultrasound (US) and microbubbles (MB) to induce temporally and spatially controlled opening of the BBB. We developed an advanced in vitro BBB model to study the impact of sonopermeation on the delivery of the prototypic polymeric drug carrier pHPMA as a larger molecule and the small molecule antiviral drug ribavirin. This was done under standard and under inflammatory conditions, employing both untargeted and RGD peptide-coated MB. The BBB model is based on human cerebral capillary endothelial cells and human placental pericytes, which are co-cultivated in transwell inserts and which present with proper transendothelial electrical resistance (TEER). Sonopermeation induced a significant decrease in TEER values and facilitated the trans-BBB delivery of fluorescently labeled pHPMA (Atto488-pHPMA). To study drug delivery under inflamed endothelial conditions, which are typical for e.g. tumors, neurodegenerative diseases and CNS infections, tumor necrosis factor (TNF) was employed to induce inflammation in the BBB model. RGD-coated MB bound to and permeabilized the inflamed endothelium-pericyte co-culture model, and potently improved Atto488-pHPMA and ribavirin delivery. Taken together, our work combines in vitro BBB bioengineering with MB-mediated drug delivery enhancement, thereby providing a framework for future studies on optimization of US-mediated drug delivery to the brain. Graphical abstract |
| Druh dokumentu: | Article Other literature type |
| Jazyk: | English |
| ISSN: | 2190-3948 2190-393X |
| DOI: | 10.1007/s13346-024-01561-6 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/38498080 https://repository.publisso.de/resource/frl:6504717 |
| Rights: | CC BY |
| Prístupové číslo: | edsair.doi.dedup.....3d0809bd8e117b39840c3aba07f3183a |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Drug delivery to central nervous pathologies is compromised by the blood-brain barrier (BBB). A clinically explored strategy to promote drug delivery across the BBB is sonopermeation, which relies on the combined use of ultrasound (US) and microbubbles (MB) to induce temporally and spatially controlled opening of the BBB. We developed an advanced in vitro BBB model to study the impact of sonopermeation on the delivery of the prototypic polymeric drug carrier pHPMA as a larger molecule and the small molecule antiviral drug ribavirin. This was done under standard and under inflammatory conditions, employing both untargeted and RGD peptide-coated MB. The BBB model is based on human cerebral capillary endothelial cells and human placental pericytes, which are co-cultivated in transwell inserts and which present with proper transendothelial electrical resistance (TEER). Sonopermeation induced a significant decrease in TEER values and facilitated the trans-BBB delivery of fluorescently labeled pHPMA (Atto488-pHPMA). To study drug delivery under inflamed endothelial conditions, which are typical for e.g. tumors, neurodegenerative diseases and CNS infections, tumor necrosis factor (TNF) was employed to induce inflammation in the BBB model. RGD-coated MB bound to and permeabilized the inflamed endothelium-pericyte co-culture model, and potently improved Atto488-pHPMA and ribavirin delivery. Taken together, our work combines in vitro BBB bioengineering with MB-mediated drug delivery enhancement, thereby providing a framework for future studies on optimization of US-mediated drug delivery to the brain. Graphical abstract |
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| ISSN: | 21903948 2190393X |
| DOI: | 10.1007/s13346-024-01561-6 |