Mesoporous silica nanostructures [Elektronische Ressource] : a versatile platform in drug-delivery and material science / Timo Lebold

Timo Lebold

Informations

• Publié par: ludwig-maximilians-universitat_munchen
• Publié le: 01 janvier 2010
• Nombre de lectures: 31
• Poids de l'ouvrage: 5 Mo

Extrait

Dissertation zur Erlangung des Doktorgrades der Fakultät für Chemie
und Pharmazie der Ludwig-Maximilians-Universität München







Mesoporous silica nanostructures:
A versatile platform in Drug-Delivery and
Material Science




Timo Lebold
aus
Miltenberg am Main


2010





ii Erklärung

Diese Dissertation wurde im Sinne von § 13 Abs. 3 bzw. 4 der Promotionsordnung vom 29.
Januar 1998 von Herrn Prof. Dr. Christoph Bräuchle betreut.




Ehrenwörtliche Versicherung

Diese Dissertation wurde selbständig, ohne unerlaubte Hilfe erarbeitet.



München, den 07. Juni 2010



………………………………………………………………
Dipl.-Chem. Timo Lebold









Dissertation eingereicht am: 15.06.2010
1. Gutachter: Prof. Dr. Christoph Bräuchle
2. Gutachter: Prof. Dr. Thomas Bein
Mündliche Prüfung am: 20.07.2010

iii




iv
Contents
1 Introduction ...................................................................................................... 1
2 Mesoporous Materials ....................................................................................... 7
2.1 Thin mesoporous silica films ........................................................................... 8
2.2 Oriented mesoporous silica through Micromoulding in Capillaries
(MIMIC) ......................................... 10
2.3 Mesoporous SBA-15 silica particles .............................................................. 12
3 Fluorescence Microscopy and Diffusion Analysis .............. 15
3.1 Fluorescence: the phenomenon and basic principles................................... 16
3.2 Fluorescence spectroscopy and microscopy ................. 20
3.2.1 Single molecule microscopy techniques ..................................................... 22
3.2.1.1 Laser Scanning Confocal Microscopy (LSCM) ............................. 22
3.2.1.2 Wide-field Fluorescence Microscopy ......................................... 24
3.2.1.3 Optical resolution and positioning accuracy: Single Particle
Tracking (SPT) ............................................. 26
3.2.1.4 Diffusion Theory ......................................... 29
3.2.2 Fluorescence recovery after photobleaching (FRAP) . 34
3.2.2.1 The basic principles of FRAP ....................................................... 35
3.2.2.2 Data evaluation ........................................... 36
3.2.2.3 Data modelling ........................................... 38

v
4 Mesoporous silica materials for drug-delivery applications .............................. 43
4.1 Introduction to Drug-Delivery ....................................................................... 44
4.2 Tuning single molecule dynamics in functionalized mesoporous silica ........ 47
4.2.1 Introduction to the sample systems: preparation and characterization ... 47
4.2.2 Single molecule trajectories ....................................................................... 54
4.2.3 Diffusion dynamics in mesoporous films .................... 56
4.2.4 Correlation of the diffusion coefficients to the pore-to-pore distance ...... 62
4.2.5 Controlling the homogeneity in the distribution of the functional
groups. ....................................................................................................... 63
4.2.6 General view on the diffusion of a individual molecule inside the
pores of functionalized mesoporous silica ................ 66
4.2.7 Conclusion .................................................................................................. 69
4.3 Nano-structured silica materials for drug-delivery of the anti-cancer
drug Doxorubicin ........................... 70
4.3.1 Introduction to the sample systems: preparation and characterization ... 71
4.3.2 Drug dynamics in the mesoporous delivery structure ............................... 73
4.3.3 Characterization of the drug release kinetics ............................................. 81
4.3.4 Live-cell measurements for testing the applicability of the delivery
system ........................................................................ 85
4.3.5 Conclusion .................................. 87
4.4 Silica films and particles with nanometer-sized channels for siRNA and
DNA delivery .................................................................. 88
4.4.1 Introduction to the sample systems: preparation and characterization ... 89
4.4.2 Thin mesoporous silica films for the delivery of siRNA .............................. 94
4.4.3 Observing oligonucleotide diffusion inside mesoporous silica delivery
particles on a single molecule level ........................................................... 98
4.4.4 Loading SBA-15 mesoporous silica particles with siRNA .......................... 102
4.4.5 Determining oligonucleotide mobility inside the delivery structure
with FRAP ................................................................................................. 107
4.4.6 Conclusion 116



vi
5 Fabricating mesoporous silica with large domains .......................................... 119
5.1 Controlling domain size in P123 templated films through adjusting the
relative humidity ......................................................................................... 120
5.1.1 Introduction to the sample systems: preparation and characterization . 120
5.1.2 Relative humidity dependent domain formation observed through
single molecule diffusion ......................................................................... 122
5.1.3 Conclusion ................................ 128
5.2 Active patterning of channel alignment in mesoporous silica through
Micromoulding in Capillaries ...................................................................... 129
5.2.1 Introduction to the sample systems: preparation and characterization . 130
5.2.1.1 The PDMS stamps ..... 131
5.2.1.2 The mesoporous silica created through pattern transfer ........ 134
5.2.2 Characterizing channel alignment in actively patterned mesoporous
silica with the help of single molecule microscopy ................................. 138
5.2.2.1 Pattern transfer from UV-stamp I ............. 139
5.2.2.2 Pattern transfer from UV-stamp II ............................................ 140
5.2.3 Conclusion ................................................................ 144
6 Summary and Outlook ................... 147
6.1 Drug-delivery using mesoporous silica hosts .............................................. 147
6.2 Creating large domains in mesoporous silica ............. 149
7 List of Abbreviations ...................................................................................... 151
8 List of Publications and Contributions to Conferences .................................... 155
8.1 Publications ................................................................. 155
8.2 Contributions to Conferences ..... 156
9 Bibliography .................................................................................................. 159
Acknowledgements .............................. 171
Curriculum Vitae .................................................................................................. 173

vii












viii
1 Introduction
Small objects can create a big impact in life. This is basically the credo of the emerging field of
nanotechnology! The physicist Richard Feynman can be considered as the father of this new
scientific discipline since already in 1959 he gave a talk at an American Physical Society
meeting at Caltech University called: “There’s Plenty of Room at the Bottom”. In his talk he
outlined the high potential of the ability to manipulate matter on an atomic scale. However,
the term “nanotechnology” was first introduced only in 1974 by Norio Taniguchi. Nowadays, it
-9generally refers to the understanding and control of matter at nanometer (10 m) dimensions.
This nano-universe shows many unique and interesting phenomena that offer intriguing
material properties and thereby pave the way for novel applications spanning nearly all
1, 2 3-5 6-10 11scientific disciplines, such as material science, chemistry, physics, biology, medicine
12-15 16, 17(“nano-medicine”) and the food industry. The work presented in this thesis would not
exist without substantial nanotechnological know-how.

18-21In this work, mesoporous silica materials are investigated. The materials possess a network
of nanometer-sized channels. They can thus act as host systems for the incorporation of a wide
amount of differently sized guest molecules. However, in contrast to zeolites, applications for
mesoporous silica materials are rare so far even though the materials show a high potential
since they are very versatile structures: their pore topologies, sizes and surfaces can be
fabricated according to the respective requirements. The entire work presented in this thesis is
devo