Interaction and toxicological studies of compounds on membrane models, cell cultures and 3D tissue models

  • The first part of the study introduces two biotechnologically produced in vitro human cell based 3D hemi-cornea test systems, which aim at the complete replacement of the Draize Eye Irritation test. These test systems allow the assessment of chemicals of any physical-chemical properties and their proper categorization in different GHS categories. The second part of the thesis describes the protective effect of brilliant blue G (BBG) on the cytotoxicity of trypan blue (TB), octenidine (Oct) and benzalkonium chloride (BAK). In the presence of TB, BBG significantly increased the cell survival of human retinal pigment epithelium cells, whereas at the same concentrations TB alone led to considerable cell damage. In the mixture with BAK, a widely used preservative in ophthalmologic solutions, or Oct, an antiseptic used for skin and wound disinfection, BBG decreased the cytotoxic effects of the two compounds on human corneal epithelial cells. A third part of the present work includes two closely related studies. The first study describes the interaction of halogenated dodecaborate clusters with liposomal membranes, characterized by using different biophysical techniques. The measurements show a strong interaction of the cluster molecules with the liposomes, which led to morphological changes of the lipids and leakage of the liposomal content. As the toxicity of the clusters on mammalian cells was not significantly high, the use of these molecules is proposed for the targeted release of drugs from liposomes used in cancer therapy. In a second study the association and uptake of liposomes containing the dodecaborate cluster lipid in endothelial and cancer cell lines is described. The association was cell type dependent and HUVEC (endothelial) cells showed the strongest uptake of lipids. The fluorescent microscopy images showed uptake for both boron-lipid and fluorescent marker lipid, even when the liposomes were sterically stabilized by pegylation.

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Publishing Institution:IRC-Library, Information Resource Center der Jacobs University Bremen
Granting Institution:Jacobs Univ.
Author:Melinda Bartok
Referee:Detlef Gabel, Stephan Reichl, Mathias Winterhalter, Maria Engelke
Advisor:Detlef Gabel
Persistent Identifier (URN):urn:nbn:de:gbv:579-opus-1002480
Document Type:PhD Thesis
Language:English
Date of Successful Oral Defense:2014/10/07
Year of Completion:2014
Date of First Publication:2015/01/15
PhD Degree:Biochemical Engineering
School:SES School of Engineering and Science
Library of Congress Classification:T Technology / TP Chemical technology / TP248.13-248.65 Biotechnology / TP248.3 Biochemical engineering. Bioprocess engineering
Call No:Thesis 2014/40

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