Nanoparticles for RNA interference: novel preclinical formulations for siRNA mediated gene therapy
Saved in:
| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
München
Hut
2010
|
| Edition: | 1. Aufl. |
| Series: | Pharmazeutische Technologie
|
| Subjects: | |
| Online Access: | Volltext https://nbn-resolving.org/urn:nbn:de:bvb:19-113293 Inhaltsverzeichnis |
| Physical Description: | XVI, 206 S. Ill., graph. Darst. 210 mm x 148 mm, 341 gr. |
| ISBN: | 9783868533446 |
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MARC
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| 008 | 100312s2010 ad|| m||| 00||| eng d | ||
| 015 | |a 10,N11 |2 dnb | ||
| 016 | 7 | |a 1000747344 |2 DE-101 | |
| 020 | |a 9783868533446 |c PB. : EUR 42.00 |9 978-3-86853-344-6 | ||
| 024 | 3 | |a 9783868533446 | |
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| 100 | 1 | |a Schultes, Stephan Johannes Baptist |d 1979- |e Verfasser |0 (DE-588)140761551 |4 aut | |
| 245 | 1 | 0 | |a Nanoparticles for RNA interference |b novel preclinical formulations for siRNA mediated gene therapy |c Stephan Johannes Baptist Schultes |
| 250 | |a 1. Aufl. | ||
| 264 | 1 | |a München |b Hut |c 2010 | |
| 300 | |a XVI, 206 S. |b Ill., graph. Darst. |c 210 mm x 148 mm, 341 gr. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 490 | 0 | |a Pharmazeutische Technologie | |
| 502 | |a Zugl.: München, Univ., Diss., 2009 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
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| 856 | 4 | 1 | |u http://edoc.ub.uni-muenchen.de/11329/ |x Verlag |z kostenfrei |3 Volltext |
| 856 | 4 | |u https://nbn-resolving.org/urn:nbn:de:bvb:19-113293 |x Resolving-System | |
| 856 | 4 | 2 | |m Digitalisierung UB Regensburg |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=018967155&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 912 | |a ebook | ||
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Record in the Search Index
| _version_ | 1804141130103652352 |
|---|---|
| adam_text | Table
of Contents
ABSTRACT
1
1
GENERAL INTRODUCTION
3
1.1
Endothelial related diseases
3
1.2
siKNA and the principle of
RNA
interference
g
13
RIVA
interference in research and therapy
13
1.4
Viral and non-viral gene delivery
14
1.5
Namiparficlcs: definitions, history and current state of knowledge
16
1.6
Gelatin based nanoparticles as colloidal drug delivery vectors
18
1.7
Body distribution of nanoparticles
19
1.8
Nanoparticle modifications
20
1.9
In-vitro and
іи
-vivo
models
23
1.10
Barriers to gene transfer
25
1.11
Nanoparticles for siRNA mediated R!4A interference
27
1.12
Goal of the thesis
29
2
MATERIALS AND METHODS
31
2.1
Nanoparticle
pré-formulation
studies
31
2.1.1
Chemicals and reagents
31
2.1.2
Materials
33
2.1.3
Formulation of unmodified gelatin nanoparticles
35
2.1.4
Formulation of cationic gelatin nanoparticles
35
2.1.5
Formulation
of diethyl-amino-elnanoi-dextran and cholamine modified gelatin Banoparticles
36
2.1.6
Formulation of human serum albumin nanoparticles
38
2.1.7
Formulation of polybutylcyanoacrylate nanoparticles
38
2.1.8
Formulation of chitosan nanoparticles
39
2.1.8.1
Preparation ofiow molecular weight chitosan
39
2.1.8.2
Synthesis of
thiobutylamidůie
and N-acerylcysteine modified chitosan
39
2.1.8.3
Preparation of unmodified and thiolated chitosan nanoparticles
40
2
J
Pojt-formuMtíímmodifkítionof
n«aop*rticles
40
2.2.1
Methyiation and acetyiation
40
2.2.1.1
Methyiation
40
2.2.1.2
Acetyiation
41
2.2.2
Fluorescence labeling
41
2.2.3
Poiysorbete and polyethylene
glycol
modification
44
2.2.4
Polyethylene imine modification
45
2.2.5
Melittm modification
45
23
Analytic«
48
2.3
Л
Chemicals and
re&gents
48
DC
49
2.3.2
Materials
Λ
2.3.3
Asymmetric flow field-flow fractionation
2.3.3.1
Setup and function
.
2.3.3.2
Asymmetric flow field-flow
fractìonatìon
of gelatins
2.3.3.3
Asymmetric flow field-flow
fractìonatìon
of
chìtosans ^
2.3.3.4
Molecular weight determination via AF4
2.3.4
Lyophilizationofchìtosannanopartìcles
2.3.5
Chitosan sulfhydryl-group and disulfide-bond quantification
2.3.6
Automatic microviscosimetry
2.3.7
Photon correlation spectroscopy
2.3.8
Electrophoretic mobility measurements
2.3.9
Static light scattering spectroscopy
2.3.10
Nuclear magnetic resonance spectroscopy
2.3.11
Scanning electron microscopy
2.3.12
siRNA loading determination via ultra-violet-absorption ™
2.3.13
siKNA loading determination via gel shift assay
2.3.14
Characterization of Melittin complexes
*
2.3.15
Confocal laser scanning microscopy
2.3.16
Endotoxin assay
62
2.3.17 Determination
of process yield
2.3.18
Storage conditions during stability studies
2.4
In-vitro models f?
2.4.1
Cell culture
2.4.1.1
Chemicals and reagents
Ґ.
2.4.1.2
Materials
°Ί
2.4.1.3
Cell lines
Ь
2.4.1.4
Cultivation of cell lines °°
2.4.1.5
Particle stability in cell culture medium
2.4.1.6
Metabolic activity of luciferase silenced cells zz
2.4.1.7
Cytotoxicity via microscopic observations
2,
2.4.2
How model °7
2.4.3
Fluorescence activated cell sorting analysis of VEGFR expression ¡?
2.4.4
Coulter counter analysis of blood cells
2.5
In-vivo models I?
2.5.1
Chemicals and reagents Z?
2.5.2
Hamster dorsal skin fold chamber model
2.5.3
Mouse cremaster model
2.5.4
Mouse arthritic knee model
2.5.5
Mouse whole body imaging
2.5.6
Pharmcokinetic studies °
2.6
siRNA mediated gene silencing and protein knock-down jj
2.6.1
Chemicals and reagents
2.6.2
Biological activity of nanoparticles 82
3
RESULTS AND DISCUSSION
83
3.1
N»nop>rtick
formulation
ю
3.2 Nanopaiücle
fluorescence lïbcling
М
3
J
Naaopaiüclc
advancements with DEA&dextran
**
3.4
Additìooal
nanopartide
modifkarJoos 10°
3.5
Naaopartide and polymer analytics m
3.5.1
Automatic microviscosimetry
1
3.5.2
Asymmetrie
flow field-flow fractionation of gelatins
103
3.5.3
Asymmetric flow field-flow ftactionation of chitosans
108
3.5.4
Cbitosan sulihydryl-group and
disulfîde-bond
quantification
110
3.5.5
Asymmetric flow field-flow fractionation of DEAE-dextran
112
3.5.6
Nuclear magnetic resonance spectroscopy of modified gelatins
115
3.6
siRNA containing gelatin nanoparticJcs (SICONs)
118
3.7
Sandwich nanopaiticlc formulation witb aMelittinconstruct
121
3.8
Storage stability of unloaded and si
RNA
loaded gelatin nanoparlicles
128
3.9
Endotoiin assay
129
3.10
In-vitro models
131
3.10.1
Traditional static conditions versus novel flow conditions cell culture model
131
3.10.1.1
Toxicity
screening
135
3.10.1.2
Medium influence
136
3.10.1.3
Flow and shear stress influence
137
3.10.2
VEGF-studies
138
3.10.2.1
FACS analysis of
VEGFR2
overexpression in
HEK
293 /
KDR cells
138
3.11
In-vivo models
140
3.11.1
Hamster dorsal skin fold chamber model
140
3.11.2
Mouse cremaster model
146
3.11.3
Mouse antigen induced arthritic knee model
149
3.11.4
Pharmacokinetics and whole body imaging
151
3.12
In-vitro
/
in-vivo correlation
160
3.13
Application of siRNA containing gelatin nanoparticles for gene delivery
161
4
SUMMARY AND OUTLOOK
171
5
FINAL CONCLUSION
173
REFERENCES
177
PUBLICATIONS
203
Original Papers
203
Application Notes
203
Oral Presentations
203
Poster
Présentations
204
CURRICULUM
VITAE
205
XI
|
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| author_facet | Schultes, Stephan Johannes Baptist 1979- |
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| discipline | Medizin |
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| format | Thesis Book |
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| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV036075981 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T22:10:58Z |
| institution | BVB |
| isbn | 9783868533446 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-018967155 |
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| physical | XVI, 206 S. Ill., graph. Darst. 210 mm x 148 mm, 341 gr. |
| psigel | ebook |
| publishDate | 2010 |
| publishDateSearch | 2010 |
| publishDateSort | 2010 |
| publisher | Hut |
| record_format | marc |
| series2 | Pharmazeutische Technologie |
| spelling | Schultes, Stephan Johannes Baptist 1979- Verfasser (DE-588)140761551 aut Nanoparticles for RNA interference novel preclinical formulations for siRNA mediated gene therapy Stephan Johannes Baptist Schultes 1. Aufl. München Hut 2010 XVI, 206 S. Ill., graph. Darst. 210 mm x 148 mm, 341 gr. txt rdacontent n rdamedia nc rdacarrier Pharmazeutische Technologie Zugl.: München, Univ., Diss., 2009 (DE-588)4113937-9 Hochschulschrift gnd-content Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:19-113293 http://edoc.ub.uni-muenchen.de/11329/ Verlag kostenfrei Volltext https://nbn-resolving.org/urn:nbn:de:bvb:19-113293 Resolving-System Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=018967155&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Schultes, Stephan Johannes Baptist 1979- Nanoparticles for RNA interference novel preclinical formulations for siRNA mediated gene therapy |
| subject_GND | (DE-588)4113937-9 |
| title | Nanoparticles for RNA interference novel preclinical formulations for siRNA mediated gene therapy |
| title_auth | Nanoparticles for RNA interference novel preclinical formulations for siRNA mediated gene therapy |
| title_exact_search | Nanoparticles for RNA interference novel preclinical formulations for siRNA mediated gene therapy |
| title_full | Nanoparticles for RNA interference novel preclinical formulations for siRNA mediated gene therapy Stephan Johannes Baptist Schultes |
| title_fullStr | Nanoparticles for RNA interference novel preclinical formulations for siRNA mediated gene therapy Stephan Johannes Baptist Schultes |
| title_full_unstemmed | Nanoparticles for RNA interference novel preclinical formulations for siRNA mediated gene therapy Stephan Johannes Baptist Schultes |
| title_short | Nanoparticles for RNA interference |
| title_sort | nanoparticles for rna interference novel preclinical formulations for sirna mediated gene therapy |
| title_sub | novel preclinical formulations for siRNA mediated gene therapy |
| topic_facet | Hochschulschrift |
| url | http://edoc.ub.uni-muenchen.de/11329/ https://nbn-resolving.org/urn:nbn:de:bvb:19-113293 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=018967155&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT schultesstephanjohannesbaptist nanoparticlesforrnainterferencenovelpreclinicalformulationsforsirnamediatedgenetherapy |