Modulation of pharmacokinetics of nanodimensional drug carriers

Hochschulschrift

Zusammenfassung: The principle of nanocarriers enables targeted transport of the drug to the cell. This novel drug delivery systems allow to better control side effects and increase the effectiveness of the packaged drug. Pharmacokinetics were studied in more detail for different nanocarrier systems in terms of nonspecific and targeted uptake by the reticuloendothelial system (RES). Predominantly flow cytometry and In vivo imaging (IVIS) were used. These studies allowed us to make assumptions about the effectiveness of the here investigated nanotherapeutics. The main objective of this work was to examine the effect of the co-medication of heparin on the pharmacokinetics of nanocarriers. The first chapter describes the influence of heparin on the nonspecific uptake of clinically relevant liposomal formulations into the phagocytosing cells of the RES. In vivo, high-dose intravenous heparinization promoted accumulation of Doxil®-like liposomes in the liver and spleen to a small extent. These weak changes do not suggest that a concomitant heparinization could affect liposomal therapy. In the second chapter, it was shown that heparin modulates the uptake of the proteinbased antigen shell nanovaccine, ovalbumine nanocapsule, in favor of the dendritic cells. The effect of ‘passive targeting’ could not be induced in vivo by a high-dose heparinization. The cellular biodistribution of this novel nanovaccine was described in detail for the first time. The second objective of this work was to investigate pharmacokinetics of novel designs and compositions of nanocarrier systems. The third chapter, a collaboration with the Max Planck Institute for Polymer Research, describes the biodistribution and preferential cellular uptake by Kupffer cells of the mesoporpous polydexamethason-loaded silica nanocapsule - a capsule loaded with a polymerized anti-inflammatory drug against inflammatory liver disease combining the benefits of targeting and controlled drug release. The fourth chapter, a collaboration with members of the SFB 1066, describes the establishment of a method to characterize the intracellular release of doxorubicin from de novo liposomal formulations using the Amnis® ImageStream® X Mark II. This work contributes to a better understanding of the complexity of the pharmacological properties of different nanocarrier systems.

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Maße: 30 cm
• Umfang: 189, iii Blätter
• Sprache: Englisch
• Anmerkungen: Illustrationen, Diagramme ; Literaturverzeichnis Blatt 177-185 ; Enthält deutsche und englische Zusammenfassung ; Johannes Gutenberg-Universität Mainz, Dissertation, 2021

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Mainz
• (wann): 2021
• Urheber: Haller, Adelina
• Beteiligte Personen und Organisationen: Johannes Gutenberg-Universität Mainz

Weitere Informationen

• Inhaltsverzeichnis: https://d-nb.info/1339534932/04
• Rechteinformation: Bei diesem Objekt liegt nur das Inhaltsverzeichnis digital vor. Der Zugriff darauf ist unbeschränkt möglich.
• Letzte Aktualisierung: 11.06.2025, 14:12 MESZ