Publikationsserver der Universitätsbibliothek Marburg

Titel:Entwicklung und Charakterisierung echogener Liposomen zur Targetierung von ADAM8
Autor:Sasko, Eric
Weitere Beteiligte: Bakowsky, Udo (Prof. Dr.)
Veröffentlicht:2017
URI:https://archiv.ub.uni-marburg.de/diss/z2017/0464
DOI: https://doi.org/10.17192/z2017.0464
URN: urn:nbn:de:hebis:04-z2017-04646
DDC: Pharmacology & therapeutics, prescription drugs
Titel(trans.):Development and characterization of echogenic liposomes targeting ADAM8
Publikationsdatum:2017-06-12
Lizenz:https://creativecommons.org/licenses/by-nc-sa/4.0

Dokument

Schlagwörter:
Targeting, Concanavalin A, liposomal ultrasound contrast agent, liposomal, ADAM8, ADAM8, liposomal targeting, Liposomen Ultraschallkontrastmittel, Liposomale Ultraschallkontrastmittel, ConA, ConA, Liposomale Targetierung

Zusammenfassung:
Das Ziel dieser Arbeit war die Entwicklung und Charakterisierung einer neuen, liposomalen, nanoskaligen Formulierung zur Anwendung als Ultraschallkontrastmittel mit der Eigenschaft, an die Zielstruktur ADAM8 zu binden. Hierbei wurde speziell auf die Struktur und Funktionalität der Lipidvehikel hinsichtlich der Tumor-Targetierung geachtet. Die Partikel wurden auf ihren Ultraschallkontrast in ihrer Lipidzusammensetzung und Herstellungsmethode optimiert und in verschiedenen Durchflussmodellen mit diagnostischem Ultraschall vermessen. Die Intensität des Kontrastes wurde mit der eines kommerziell erhältlichen und klinisch verwendeten Ultraschall- kontrastmittels verglichen. Die Targetierung wurden die Vehikel kovalent mit einem Targetierungsliganden verknüpft und es wurden an verschiedenen Zielstrukturen Bindungsversuche durchgeführt. Der Fokus lag auf der Targetierung von ADAM8. Die Lipid-basierten Nanopartikel erfüllten die an sie gestellten Anforderungen bezüglich Größe, Struktur, Stabliltät, Funktionalität und konnten in den Targetierungversuchen durch deutliche Anreicherung an allen Zielstrukturen, vor allem ADAM8, überzeugen.

Summary:
This thesis deals with the development and characterization of new, liposomal, nano-scaled vehicles to be used as ultrasound contrast agent. Besides that, the vehicles are used as tumor targeting devices by binding to ADAM8. Size, structure and functionality was closely determined to meet this criteria. Ultrasound contrast ability was optimized by different lipid-compositions and/or manufacturing methods.The intensity of contrast was compared to a comercially available. clinically used contrast agent. For targeting-studies, the vehicles were covalently bound to a targeting-ligand and several binding-studies on different target structures were performed, focussing ADAM8. The lipid-based nanoparticles matched criterias like size, structure, stability, functionality and proved themselves capaple of targeting several targeting-structures, including ADAM8.

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