Twin-screw extruded lipid implants for controlled protein drug delivery:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
München
Verl. Dr. Hut
2012
|
| Ausgabe: | 1. Aufl. |
| Schriftenreihe: | Pharmazeutische Technologie
|
| Schlagworte: | |
| Online-Zugang: | https://nbn-resolving.org/urn:nbn:de:bvb:19-146306 kostenfrei Inhaltsverzeichnis |
| Beschreibung: | 205, XI S. Ill., graph. Darst. |
| ISBN: | 9783843905831 |
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| 245 | 1 | 0 | |a Twin-screw extruded lipid implants for controlled protein drug delivery |c Gerhard Ludwig Sax |
| 250 | |a 1. Aufl. | ||
| 264 | 1 | |a München |b Verl. Dr. Hut |c 2012 | |
| 300 | |a 205, XI S. |b Ill., graph. Darst. | ||
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| 650 | 0 | 7 | |a Lipide |0 (DE-588)4035873-2 |2 gnd |9 rswk-swf |
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Datensatz im Suchindex
| _version_ | 1804149504751960064 |
|---|---|
| adam_text | IMAGE 1
TABLE OF CONTENT
TABLE OF CONTENT I
I. GENERAL INTRODUCTION 1
1. CONTROLLED RELEASE SYSTEMS FOR PHARMACEUTICAL PEPTIDES AND PROTEINS 5
1.1. DEFINITION OF CONTROLLED RELEASE 5
1.2. CURRENTLY MARKETED PEPTIDE AND PROTEIN DEPOT FORMULATIONS 6
2. MATRIX MATERIALS FOR THE PREPARATION OF PROTEIN CONTAINING SUSTAINED
RELEASE DEVICES .. 9
3. LIPIDS AS MATRIX MATERIALS FOR THE PREPARATION OF PROTEIN CONTAINING
SUSTAINED RELEASE
DEVICES 13
3.1. LIPID BASED DRUG DELIVERY SYSTEMS 13
4. MECHANISM OF RELEASE FROM IMPLANT MATRICES 31
4.1. MECHANISM OF RELEASE FROM TRIGLYCERIDE BASED IMPLANTS 33
4.2. MECHANISM OF RELEASE FROM COMPRESSED AND TSC-EXTRUDED IMPLANTS 34
II. AIM OF THE THESIS 37
III. TWIN-SCREW EXTRUDATES FOR THE SUSTAINED RELEASE OF A THERAPEUTIC
ANTIBODY 39
1. INTRODUCTION 39
2. MATERIALS AND METHODS 41
2.1. MATERIALS 41
2.2. QUANTIFICATION OF MABB 41
2.3. PRECIPITATION AND RE-DISSOLUTION STUDIES 41
2.4. ANTIBODY SOLUBILITY STUDIES IN THE PRESENCE OF PEG 6000 42
2.5. SODIUM DODECYL SULFATE POLYACRYLAMIDE GEL ELECTROPHORESIS
(SDS-PAGE) 42
2.6. LYOPHILIZATION OF MABB 43
2.7. LYOPHILIZATION OF PEG 6000 44
HTTP://D-NB.INFO/1026135710
IMAGE 2
2.8. COULOMETRIC KARL-FISCHER HEADSPACE TITRATION 44
2.9. PREPARATION OF LIPID IMPLANTS BY TSC-EXTRUSION 44
2.10. ANTIBODY RELEASE TESTS FROM TSC-EXTRUDATES 45
2.11. SCANNING ELECTRON MICROSCOPY 46
3. RESULTS AND DISCUSSION 47
3.1. PRELIMINARY PRECIPITATION STUDIES 47
3.2. ANTIBODY SOLUBILITY STUDIES IN THE PRESENCE OF VARIOUS AMOUNTS OF
PEG 6000 47
3.3. MABB PRECIPITATION AND RE-DISSOLUTION AFTER LONG-TERM INCUBATION 49
3.4. PRODUCTION OF LYOPHILIZED OF MABB POWDER 52
3.5. MABB RELEASE STUDIES FROM TSC-EXTRUDED LIPID IMPLANTS 56
4. CONCLUSION 63
IV. INFLUENCE OF THE MANUFACTURING STRATEGY ON PROTEIN RELEASE KINETICS
FROM LIPID BASED
IMPLANTS 65
1. INTRODUCTION 65
2. MATERIALS AND METHODS 67
2.1. MATERIALS 67
2.2. METHODS 68
3. RESULTS 73
3.1. LYSOZYME RELEASE FROM LIPID BASED IMPLANTS 73
3.2. ASSESSMENT OF IMPLANT PORE STRUCTURE 75
3.3. X-RAY DIFFRACTION MEASUREMENTS 77
3.4. DSC-MEASUREMENTS 80
4. SUMMARY 85
V. MECHANISTIC STUDIES ON THE RELEASE OF LYSOZYME FROM TWIN-SCREW
EXTRUDED LIPID IMPLANTS
(I) - INFLUENCE OF PORE-FORMER AND LIPID COMPOSITION 87
1. INTRODUCTION 87
IMAGE 3
1.1. MATERIAL 87
1.2. METHODS 87
2. RESULTS OF THE INFLUENCE OF THE PORE-FORMING AGENT ON LYSOZYME
RELEASE 89
2.1. INFLUENCE OF PEG 4000 PARTICLE SIZE ON LYSOZYME RELEASE 89
2.2. INFLUENCE OF VISCOSITY WITHIN THE IMPLANT PORES 92
2.3. INFLUENCE OF THE DISSOLUTION RATE OF PEG 94
3. INFLUENCE OF LIPID MATRIX COMPOSITION 97
3.1. INFLUENCE OF THE RATIO BETWEEN LOW AND HIGH MELTING LIPID 97
3.2. INFLUENCE OF THE HIGH MELTING LIPID 99
3.3. INFLUENCE OF THE TYPE OF LOW-MELTING LIPID 100
4. SUMMARY AND OUTLOOK 105
VI. MECHANISTIC STUDIES ON THE RELEASE OF LYSOZYME FROM TWIN-SCREW
EXTRUDED LIPID
IMPLANTS (II) - INFLUENCE OF IMPLANT MELTING 107
1. INTRODUCTION 107
2. MATERIALS AND METHODS 109
2.1. MATERIALS 109
2.2. PREPARATION OF LIPID TWIN-SCREW EXTRUDATES (TSC-EXTRUDATES) 109
2.3. DIFFERENTIAL SCANNING CALORIMETRY (DSC) 111
2.4. WIDE-ANGLE X-RAY SCATTERING (WAXS) 111
2.5. IN-VITRO RELEASE TESTS 111
2.6. PROTEIN EXTRACTION FROM LIPID IMPLANTS 112
2.7. ASSESSMENT OF IMPLANT WEIGHT AND WEIGHT LOSS 112
2.8. SCANNING ELECTRON MICROSCOPY (SEM) 112
3. RESULTS 113
3.1. PREPARATION OF LIPID TWIN-SCREW EXTRUDATES 113
IMAGE 4
3.2. LYSOZYME RELEASE AT VARIOUS TEMPERATURES 113
3.3. LYSOZYME RELEASE FROM LIPID IMPLANTS COMPRISING VARIOUS LOW MELTING
LIPIDS 114
3.4. LYSOZYME RELEASE WITH VARIOUS AMOUNTS OF PORE FORMING AGENT 115
3.5. SCANNING ELECTRON MICROSCOPY OF TSC-EXTRUDATES AFTER IN-VITRO
RELEASE 117
3.6. RESULT OF DSC MEASUREMENTS 117
3.7. RESULTS OF X-RAY MEASUREMENTS 120
3.8. ASSESSMENT OF IMPLANT WEIGHT 122
4. DISCUSSION 123
4.1. LYSOZYME RELEASE AT VARIOUS TEMPERATURES 123
4.2. LYSOZYME RELEASE FROM IMPLANTS COMPRISING VARIOUS LOW MELTING
LIPIDS 124
4.3. LYSOZYME RELEASE FROM IMPLANTS COMPRISING VARIOUS AMOUNTS OF PORE
FORMING
AGENT 124
4.4. X-RAY DIFFRACTION MEASUREMENTS 127
5. CONCLUSION 129
VII. IN-VIVO BIODEGRADABILITY OF LIPID TWIN-SCREW EXTRUDED IMPLANTS IN
RABBITS 131
1. INTRODUCTION 131
2. MATERIALS AND METHODS 133
2.1. MATERIALS 133
2.2. PREPARATION OF LIPID IMPLANTS 133
2.3. PRELIMINARY TESTING 135
2.4. DIFFERENTIAL SCANNING CALORIMETRY (DSC) 136
2.5. SCANNING ELECTRON MICROSCOPY (SEM) 136
2.6. SELECTION OF TEST ANIMALS 136
2.7. ANIMAL TREATMENT AND IN-VIVO DEGRADATION STUDY 136
2.8. RECOVERY OF IMPLANTS AND ASSESSMENT OF IMPLANT WEIGHTS AFTER
IN-VIVO STUDY.. . 137
IMAGE 5
2.9. IN-VITRO DEGRADATION STUDY 138
3. RESULTS AND DISCUSSION 139
3.1. PRELIMINARY STUDIES 139
3.2. ANIMAL TREATMENT AND RECOVERY OF IMPLANTS 140
3.1. IN-VITRO DEGRADATION STUDY OF LIPID IMPLANTS 141
3.2. IN-VIVO DEGRADATION OF FORMULATION A 145
3.3. INFLUENCE OF THE AMOUNT OF PORE-FORMER ON THE DEGRADABILITY OF
LIPID TSC-EXTUDATES
151
3.4. INFLUENCE OF THE TYPE OF LOW-MELTING LIPID 153
4. CONCLUSION 155
VIII. LIPASE INDUCED IN-VITRO DEGRADATION STUDY WITH TSC-EXTRUDATES 157
1. INTRODUCTION 157
2. MATERIALS AND METHODS 159
2.1. MATERIALS 159
2.2. METHODS 159
3. RESULTS 165
3.1. IMPLANT DEGRADATION AFTER EMBEDDING OF LIPASE 165
3.2. SIMULTANEOUS RELEASE OF LIPASE AND LYSOZYME FROM LIPID
TSC-EXTRUDATES 168
4. CONCLUSION 175
IX. SINGLE MOLECULE FLUORESCENCE MICROSCOPY STUDIES AND RELEASE PATHWAYS
OF PROTEIN
DRUG MOLECULES FROM TRIGLYCERIDE BASED IMPLANTS 177
1. INTRODUCTION 177
2. MATERIALS AND METHODS 179
2.1. MATERIALS 179
2.2. FLUORESCENCE LABELING OF IFNA 179
IMAGE 6
2.3. PROTEIN ANALYSIS 180
2.4. PREPARATION OF IFNA LYOPHILISATES 180
2.1. PREPARATION OF LIPID TWIN-SCREW EXTRUDATES AND PROTEIN-LIPID
DISPERSIONS FOR WIDE-
FIELD FLUORESCENCE SPECTROSCOPY 180
2.2. PREPARATION OF PEG SAMPLES FOR FLUORESCENCE MICROSCOPY 182
2.3. SCANNING ELECTRON MICROSCOPY (SEM) 182
2.4. WIDE-FIELD FLUORESCENCE MICROSCOPY 182
2.5. TRACKING OF THE PROTEINS, VISUALIZATION OF THE RANDOM WALK AND
CALCULATION OF
DIFFUSION COEFFICIENTS 182
2.6. PROTEIN RELEASE STUDIES 183
3. RESULTS AND DISCUSSION 185
3.1. SCANNING ELECTRON MICROSCOPY 185
3.2. QUANTIFICATION OF FLUO-IFNA 185
3.3. IFNA RELEASE STUDIES FROM TSC-EXTRUDATES 187
3.4. IFNA RELEASE FROM PROTEIN-LIPID DISPERSIONS 188
3.5. WIDE-FIELD FLUORESCENCE MICROSCOPY OF TSC-EXTRUDATES 189
3.6. DIFFUSION PATHWAYS OF FLUO-IFNA MOLECULES IN TSC-EXTRUDATES 192
3.7. RANDOM WALK OF IFNA MOLECULES 195
4. CONCLUSION 199
X. FINAL SUMMARY 201
REFERENCES I
|
| any_adam_object | 1 |
| author | Sax, Gerhard Ludwig 1980- |
| author_GND | (DE-588)1027243568 |
| author_facet | Sax, Gerhard Ludwig 1980- |
| author_role | aut |
| author_sort | Sax, Gerhard Ludwig 1980- |
| author_variant | g l s gl gls |
| building | Verbundindex |
| bvnumber | BV040446117 |
| collection | ebook |
| ctrlnum | (OCoLC)815935952 (DE-599)BVBBV040446117 |
| dewey-full | 610 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 610 - Medicine and health |
| dewey-raw | 610 |
| dewey-search | 610 |
| dewey-sort | 3610 |
| dewey-tens | 610 - Medicine and health |
| discipline | Medizin |
| edition | 1. Aufl. |
| format | Thesis Book |
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| oclc_num | 815935952 |
| open_access_boolean | 1 |
| owner | DE-91 DE-BY-TUM DE-12 DE-384 DE-473 DE-BY-UBG DE-703 DE-1051 DE-824 DE-29 DE-19 DE-BY-UBM DE-1049 DE-92 DE-739 DE-898 DE-BY-UBR DE-355 DE-BY-UBR DE-706 DE-20 DE-1102 |
| owner_facet | DE-91 DE-BY-TUM DE-12 DE-384 DE-473 DE-BY-UBG DE-703 DE-1051 DE-824 DE-29 DE-19 DE-BY-UBM DE-1049 DE-92 DE-739 DE-898 DE-BY-UBR DE-355 DE-BY-UBR DE-706 DE-20 DE-1102 |
| physical | 205, XI S. Ill., graph. Darst. |
| psigel | ebook |
| publishDate | 2012 |
| publishDateSearch | 2012 |
| publishDateSort | 2012 |
| publisher | Verl. Dr. Hut |
| record_format | marc |
| series2 | Pharmazeutische Technologie |
| spelling | Sax, Gerhard Ludwig 1980- Verfasser (DE-588)1027243568 aut Twin-screw extruded lipid implants for controlled protein drug delivery Gerhard Ludwig Sax 1. Aufl. München Verl. Dr. Hut 2012 205, XI S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Pharmazeutische Technologie Zugl.: München, Univ., Diss., 2012 Biologischer Abbau (DE-588)4145625-7 gnd rswk-swf Kontrollierte Wirkstofffreisetzung (DE-588)4165181-9 gnd rswk-swf Doppelschneckenextruder (DE-588)4250473-9 gnd rswk-swf Proteine (DE-588)4076388-2 gnd rswk-swf Therapeutisches System (DE-588)4267580-7 gnd rswk-swf Lipide (DE-588)4035873-2 gnd rswk-swf Implantat (DE-588)4026658-8 gnd rswk-swf Arzneistoffträger (DE-588)4278196-6 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Doppelschneckenextruder (DE-588)4250473-9 s Lipide (DE-588)4035873-2 s Arzneistoffträger (DE-588)4278196-6 s Kontrollierte Wirkstofffreisetzung (DE-588)4165181-9 s Proteine (DE-588)4076388-2 s Therapeutisches System (DE-588)4267580-7 s DE-604 Implantat (DE-588)4026658-8 s Biologischer Abbau (DE-588)4145625-7 s Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:19-146306 https://nbn-resolving.org/urn:nbn:de:bvb:19-146306 Resolving-System http://edoc.ub.uni-muenchen.de/14630 Verlag kostenfrei DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025293850&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Sax, Gerhard Ludwig 1980- Twin-screw extruded lipid implants for controlled protein drug delivery Biologischer Abbau (DE-588)4145625-7 gnd Kontrollierte Wirkstofffreisetzung (DE-588)4165181-9 gnd Doppelschneckenextruder (DE-588)4250473-9 gnd Proteine (DE-588)4076388-2 gnd Therapeutisches System (DE-588)4267580-7 gnd Lipide (DE-588)4035873-2 gnd Implantat (DE-588)4026658-8 gnd Arzneistoffträger (DE-588)4278196-6 gnd |
| subject_GND | (DE-588)4145625-7 (DE-588)4165181-9 (DE-588)4250473-9 (DE-588)4076388-2 (DE-588)4267580-7 (DE-588)4035873-2 (DE-588)4026658-8 (DE-588)4278196-6 (DE-588)4113937-9 |
| title | Twin-screw extruded lipid implants for controlled protein drug delivery |
| title_auth | Twin-screw extruded lipid implants for controlled protein drug delivery |
| title_exact_search | Twin-screw extruded lipid implants for controlled protein drug delivery |
| title_full | Twin-screw extruded lipid implants for controlled protein drug delivery Gerhard Ludwig Sax |
| title_fullStr | Twin-screw extruded lipid implants for controlled protein drug delivery Gerhard Ludwig Sax |
| title_full_unstemmed | Twin-screw extruded lipid implants for controlled protein drug delivery Gerhard Ludwig Sax |
| title_short | Twin-screw extruded lipid implants for controlled protein drug delivery |
| title_sort | twin screw extruded lipid implants for controlled protein drug delivery |
| topic | Biologischer Abbau (DE-588)4145625-7 gnd Kontrollierte Wirkstofffreisetzung (DE-588)4165181-9 gnd Doppelschneckenextruder (DE-588)4250473-9 gnd Proteine (DE-588)4076388-2 gnd Therapeutisches System (DE-588)4267580-7 gnd Lipide (DE-588)4035873-2 gnd Implantat (DE-588)4026658-8 gnd Arzneistoffträger (DE-588)4278196-6 gnd |
| topic_facet | Biologischer Abbau Kontrollierte Wirkstofffreisetzung Doppelschneckenextruder Proteine Therapeutisches System Lipide Implantat Arzneistoffträger Hochschulschrift |
| url | https://nbn-resolving.org/urn:nbn:de:bvb:19-146306 http://edoc.ub.uni-muenchen.de/14630 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025293850&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT saxgerhardludwig twinscrewextrudedlipidimplantsforcontrolledproteindrugdelivery |