Development of controlled release microparticles for vaccine delivery:
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| Format: | Thesis Book |
| Language: | English German |
| Published: |
2014
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Item Description: | Zsfassung in engl. und dt. Sprache |
| Physical Description: | VIII, 178 S. Ill., graph. Darst. |
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| adam_text | DEVELOPMENT OF CONTROLLED RELEASE
MICROPARTICLES FOR VACCINE
DELIVERY
DER NATURWISSENSCHAFTLICHEN FAKULTDT
DER FRIEDRICH-ALEXANDER-UNIVERSITAT ERLANGEN-NURNBERG
ZUR
ERLANGUNG DES DOKTORGRADES DR. RER. NAT.
VORGELEGT VON
FELIX WOLF
AUS ALTDORF B. NURNBERG
HTTP://D-NB.INFO/1053435428
TABLE OF CONTENTS I
TABLE OF CONTENTS
1 INTRODUCTION... 1
2 MICROENCAPSULATED PROTEINS AS DRUG DELIVERY SYSTEMS.. 4
2.1 WHY MICROENCAPSULATION OF PROTEINS? 4
2.2 REQUIREMENTS FOR MICROPARTICULATE PROTEIN DELIVERY
SYSTEMS 6
2.3 POLYMERS USED FOR CONTROLLED
RELEASE 8
2.3.1 POLYMER DEGRADATION 11
2.4 TECHNIQUES FOR THE MICROENCAPSULATION
OF PROTEINS 14
2.4.1 EMULSION-SOLVENT EVAPORATION/EXTRACTION METHODS 14
2.4.2 PHASE SEPARATION (COACERVATION) 17
2.4.3 SPRAY DRYING 18
2.4.4 PROLEASE TECHNOLOGY 19
2.4.5 INTERFACIAL PHASE SEPARATION 20
2.4.6 FURTHER METHODS 22
2.4.7 SUMMARY AND OBJECTIVES OF THIS THESIS 23
3 CONTROLLED RELEASE OF VACCINES 26
3.1 IMMUNE RESPONSE TO PROTEIN-LOADED
MICROSPHERES 26
3.2 STABILITY ISSUES OF CONTROLLED-RELEASE
PROTEIN DELIVERY SYSTEMS
....
28
3.2.1 STRUCTURE OF PROTEINS 29
3.2.2 PROTEIN INSTABILITIES :..
32
3.2.3 PROTEIN INSTABILITIES WITHIN PLGA DDS 34
3.3 CHALLENGES IN MAINTAINING
ANTIGEN INTEGRITY 37
3.3.1 ADDITION OF EXCIPIENTS 38
3.3.2 FURTHER STRATEGIES 43
4 MATERIALS AND METHODS. 46
4.1 BIODEGRADABLE POLYMERS 46
4.2 MODEL SUBSTANCES 46
4.3 CROSS-REACTIVE MATERIAL 197 (CRMI
97
) 48
4.3.1 HISTORICAL BACKGROUND 48
N TABLE OF CONTENTS
4.3.2 APPLICATION OF CRMM 48
4.3.3 STRUCTURE 50
4.4 EXCIPIENTS AND REAGENTS 51
4.5 SPRAY DRYING PROCEDURE 53
4.5.1 EXPERIMENTAL SETUP FOR DOE APPROACH 53
4.5.2 SPRAY DRYING OF PREFORMED EMULSIONS 54
4.5.3 PRELIMINARY MICROENCAPSULATION EXPERIMENTS 54
4.5.4 IN SITU MICROENCAPSULATION EXPERIMENTS 55
4.6 DESIGN OF EXPERIMENTS (DOE)
APPROACH 56
4.7 ANALYTICAL METHODS 56
4.7.1 PARTICLE SIZE DISTRIBUTION 56
4.7.2 SCANNING ELECTRON MICROSCOPY 57
4.7.3 DIFFERENTIAL SCANNING CALORIMETRY 57
4.7.4 RESIDUAL MOISTURE, KARL-FISCHER TITRATION 57
4.7.5 LIGHT MICROSCOPY 58
4.7.6 CONFOCAL LASER SCANNING MICROSCOPY 58
4.7.7 BRADFORD ASSAY 58
4.7.8 RELEASE TESTING 59
4.7.9 FLUORESCENCE SPECTROSCOPY 60
4.7.10 SIZE EXCLUSION CHROMATOGRAPHY (SEC) 61
4.7.11 UV/VIS SPECTROSCOPY 61
4.7.12 VISUALIZATION OF ANTIGEN PRECIPITATES 62
4.7.13 FOURIER TRANSFORM INFRARED SPECTROSCOPY (FTIR) 62
4.7.14 VISCOSITY MEASUREMENTS 63
5 RESULTS AND DISCUSSION 64
5.1 CONTROL OF PARTICLE SIZE DURING
SPRAY DRYING 64
5.1.1 PRELIMINARY TRIALS 64
5.1.2 DESIGN OF EXPERIMENTS (DOE) APPROACH 66
5.1.2.1 DATA ANALYSIS PROCEDURE 68
5.1.2.2 PARTICLE SIZE DISTRIBUTION 72
5.1.2.3 MORPHOLOGY 78
5.1.2.4 YIELD. 79
TABLE OF CONTENTS III
5.1.2.5 GLASS TRANSITION TEMPERATURE 81
5.1.2.6 OUTLET TEMPERATURE 83
5.1.3 OPTIMIZATION OF PARTICLE SIZE AND DESIGN SPACE ESTIMATION 84
5.1.4 MAXIMUM POLYMER CONCENTRATION FOR SPRAY-DRYING 87
5.1.5 COMPARISON WITH PROCEPT SPRAY DRYER 88
5.2 IN SITU MICROENCAPSULATION: FORMATION OF PLACEBO
PARTICLES 91
5.2.1 SPRAY DRYING OF PREFORMED W/O-EMULSIONS 91
5.2.2 PRELIMINARY EXPERIMENTS FOR IN SITU MICROENCAPSULATION 95
5.2.3 IN SITU MICROENCAPSULATION 97
5.2.3.1 EVALUATION OF PROCESS PARAMETERS 97
5.2.3.2 ENCAPSULATION EFFICIENCY 109
5.2.3.3 RELEASE OF MODEL SUBSTANCES 117
5.3 ANTIGEN STABILITY DURING
MICROENCAPSULATION 123
5.3.1 MICROENCAPSULATION OF CRM^ 123
5.3.2 ATOMIZATION STEP 123
5.3.3 DRYING STEP 131
5.3.4 INFLUENCE OF ORGANIC SOLVENT 133
5.3.5 ANTIGEN STABILIZATION 138
5.3.5.1 ADDITION OF THICKENING AGENTS 138
5.3.5.2 EXCHANGE OF DISACCHARIDE 140
5.3.5.3 ADDITION OF BOVINE SERUM ALBUMIN 140
5.3.5.4 ADDITION OF POLYETHYLENE GLYCOL 400 141
5.3.6 CRMWLOADED MICROPARTICLES 143
6 CONCLUSIONS 152
7 ZUSAMMENFASSUNG UND AUSBLICK 156
8 REFERENCES 161
9 CURRICULUM VTTAE 178
|
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| dewey-ones | 570 - Biology 610 - Medicine and health |
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| dewey-search | 570 610 |
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| dewey-tens | 570 - Biology 610 - Medicine and health |
| discipline | Biologie Medizin |
| format | Thesis Book |
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| spelling | Wolf, Felix 1984- Verfasser (DE-588)105309504X aut Development of controlled release microparticles for vaccine delivery vorgelegt von Felix Wolf 2014 VIII, 178 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Zsfassung in engl. und dt. Sprache Erlangen-Nürnberg, Univ., Diss., 2014 Mikropartikel (DE-588)4336527-9 gnd rswk-swf Kontrollierte Wirkstofffreisetzung (DE-588)4165181-9 gnd rswk-swf Impfstoff (DE-588)4026655-2 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Kontrollierte Wirkstofffreisetzung (DE-588)4165181-9 s Mikropartikel (DE-588)4336527-9 s Impfstoff (DE-588)4026655-2 s DE-188 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027396123&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Wolf, Felix 1984- Development of controlled release microparticles for vaccine delivery Mikropartikel (DE-588)4336527-9 gnd Kontrollierte Wirkstofffreisetzung (DE-588)4165181-9 gnd Impfstoff (DE-588)4026655-2 gnd |
| subject_GND | (DE-588)4336527-9 (DE-588)4165181-9 (DE-588)4026655-2 (DE-588)4113937-9 |
| title | Development of controlled release microparticles for vaccine delivery |
| title_auth | Development of controlled release microparticles for vaccine delivery |
| title_exact_search | Development of controlled release microparticles for vaccine delivery |
| title_full | Development of controlled release microparticles for vaccine delivery vorgelegt von Felix Wolf |
| title_fullStr | Development of controlled release microparticles for vaccine delivery vorgelegt von Felix Wolf |
| title_full_unstemmed | Development of controlled release microparticles for vaccine delivery vorgelegt von Felix Wolf |
| title_short | Development of controlled release microparticles for vaccine delivery |
| title_sort | development of controlled release microparticles for vaccine delivery |
| topic | Mikropartikel (DE-588)4336527-9 gnd Kontrollierte Wirkstofffreisetzung (DE-588)4165181-9 gnd Impfstoff (DE-588)4026655-2 gnd |
| topic_facet | Mikropartikel Kontrollierte Wirkstofffreisetzung Impfstoff Hochschulschrift |
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