DARWIN Digitale Dissertationen German Version Strich

FU Berlin
Digitale Dissertation

Kerstin Tabatt :
Pharmaceutical-Biotechnological Applications of Solid Lipid Nanoparticles (SLN)
Vaccine Adjuvants and Gene Transfer Vehicles
Pharmazeutisch-biotechnologische Anwendungen von Festen Lipidnanopartikeln (SLN)

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Abstract

The first part is dealing with investigations concerning the application of Solid Lipid Nano-particles (SLN) as a vaccine adjuvant. For this purpose we vaccinated hens under addition of SLN and determined the egg yolk concentrations of IgY. The advantage of this technique is the bloodless sample preparation. The adjuvant effect was compared to freund's complete/incomplete adjuvant (FCA/FIA) and to the vaccine without any adjuvant. The SLN induced characteristic changes of the chronological titer development. This is an indication of an adjuvant effect. The tissue tolerability was very good. Antibody titers were enhanced only slightly. Further experiments should be performed to optimise the vaccination protocol and to investigate the effect of different antigenes. The second part is about the development of cationic SLN as a new transfection agent. Based on first experiments the formulation was optimised. For this purpose an in vitro transfection model based on Cos-1 cells was employed. The optimisation lead to a very efficient formulation with good tolerability. The cationic lipids employed determined cytotoxicity: one-tailed cationic lipids showed high cytotoxicity, while two-tailed cationic lipids were well tolerated. Transfection efficiency was dependent on the cationic lipid and the matrix lipid used. Cationic SLN showed very good storage stability. Steam sterilization was possible. SLN and cationic liposomes revealed comparable transfection efficiencies. Combination of cationic SLN with the nuclear localisation signal TAT2 increased transfection efficiency hundredfold.

Table of Contents

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0. Titelblatt, Inhaltsverzeichnis
1. Einleitung 1
1.1 Nano- und Mikropartikuläre Arzneistoffträgersysteme 1
1.2 Feste Lipidnanopartikel 2
1.3 Ziele der Dissertation 3
2. Material und Methoden 4
2.1 Methoden 4
2.2 Materialien 20
3. SLN als Impstoffadjuvantien 30
3.1 Einleitung 30
3.2 SLN als Adjuvans für die Vakzinierung von Hennen 37
3.3 Untersuchungen zum Einfluß der Adjuvansmenge und Partikelgröße auf die Immunantwort am Huhnmodell 46
3.4 Ausblick 65
4. SLN als Gentransfervehikel 66
4.1 Einleitung 66
4.2 Formulierungsentwicklung und -optimierung I 75
4.3 Formulierungsentwicklung und -optimierung II 119
4.4 Vergleich mit Liposomen 153
4.5 Weitergehende physikalische Charakterisierung 159
4.6 Steigerung der Transfektionseffiziens durch den Einsatz von Kernlokalisationssequenzen (NLS) 166
5. Zusammenfassung 172
6. Literaturverzeichnis 175
7. Anhang 191
7.1 Verwendete Abkürzungen 191
7.2 Liefernachweise der Geräte und Materialien 194
7.3 Verwendete Puffersubstanzen und Lösungen 198
7.4 Publikationen und Kongreßbeiträge 200
7.5 Danksagung 202
7.6 Lebenslauf 203

More Information:

Online available: http://www.diss.fu-berlin.de/2003/6/indexe.html
Language of PhDThesis: german
Keywords: Solid lipid nanoparticles, non-viral transfection, vaccine adjuvants, cationic lipids
DNB-Sachgruppe: 30 Chemie
Date of disputation: 13-Dec-2002
PhDThesis from: Fachbereich Biologie, Chemie, Pharmazie, Freie Universität Berlin
First Referee: Prof. Dr. Rainer H. Müller
Second Referee: Prof. Dr. Claus-Michael Lehr
Contact (Author): ktabatt@zedat.fu-berlin.de
Contact (Advisor): mpharma@zedat.fu-berlin.de
Date created:25-Dec-2002
Date available:16-Jan-2003

 

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