臺灣博碩士論文加值系統

致謝詞 i
中文摘要 ii
Abstract iv
Table of Contents vi
List of tables xii
List of figures xiii
Abbreviate Table xvi
Chapter 1: Background Introduction 1
1.1 Curcumin 1
1.1.1 Introductions of Curcumin 1
1.1.2 Safety and Limitation of Curcumin in Pre-clinical and Clinical Applications 2
1.2 Drug Delivery Systems 3
1.2.1 Self-assembly Drug Delivery Systems 5
1.2.2 Micro-capsule Emulsifying Drug Delivery Systems 7
1.3 Solidification Process 7
1.4 Pharmaceutical Industry and Environmental Issues 8
1.5 Motivation 10
Chapter 2: Materials 11
2.1 Chemicals and Reagents 11
2.2 Cell Lines and Influenza Virus 11
2.3 Animals 12
Chapter 3: One-Pot Solidification of Self-assembly Curcumin and Its Anti-influenza A Virus Activity 13
3.1 Introduction and Motivation 13
3.1.1 Introductions of Viral Diseases 13
3.1.2 Influenza A Virus 14
3.1.3 Curcumin Inhibited the Proliferation of Influenza A Virus 15
3.1.4 Opportunity and Possibility of Formulated Curcumin for Inhibiting Influenza Virus Proliferation 16
3.2 Experimental Design and Methods 17
3.2.1 Experimental Design 17
3.2.2 Preparation of Curcumin Loaded Micelles (Cur-MSA) by Self-assembly Process 18
3.2.3 Characterization of Curcumin Loaded Self-assembly Micelles (Cur-MSA) 18
3.2.4 In Vitro Cytotoxicity 18
3.2.5 Cell Uptake Study 19
3.2.6 Virus Infection and Plaque Assay 19
3.2.7 Time-of-drug-addition Assays During Virus Infection 20
3.2.8 Preparation of Curcumin Loaded Solid Self-assembly Micelles (Cur-SMSA) by One Pot Solidification Process 21
3.2.9 Morphology of Adsorbent and Curcumin Loaded Solid Self-assembly Micelles (Cur-SMSA) 21
3.2.10 Quantitative Analysis of Curcumin 22
3.2.11 Water Solubility Study 22
3.2.12 In Vitro Release Profile 22
3.2.13 Stability of Curcumin Loaded Self-assembly Micelles (Cur-SMSA) in Different pH Buffers 23
3.2.14 Curcumin for Use in Pharmaceutical Formulations 23
3.2.15 Statistical analysis 24
3.3 Results 25
3.3.1 Characterization of Curcumin Loaded Self-assembly Micelles (Cur-MSA) 25
3.3.2 In Vitro Cytotoxicity Study of Curcumin Loaded Self-assembly Micelles (Cur-MSA) 28
3.3.3 Cell Uptake Study of Curcumin Loaded Self-assembly Micelles (Cur-MSA) by Laser Scanning Confocal Microscopy (LSCM) 29
3.3.4 Anti-influenza Activity of Micelle, Curcumin and Curcumin Loaded Self-assembly Micelles (Cur-MSA) 31
3.3.5 Investigation of Anti-influenza Mechanism of Curcumin Loaded Self-assembly Micelles (Cur-MSA) 33
3.3.6 Morphology of Adsorbent and Curcumin Loaded Solid Self-assembly Micelles (Cur-SMSA) 35
3.3.7 Water Solubility Study of Curcumin Loaded Self-assembly Micelles (Cur-MSA) and Curcumin Loaded Solid Self-assembly Micelles (Cur-SMSA) 36
3.3.8 In Vitro Release Profile of Curcumin Loaded Self-assembly Micelles (Cur-MSA) and Curcumin Loaded Solid Self-assembly Micelles (Cur-SMSA) 38
3.3.9 Stability Study of Curcumin Loaded Self-assembly Micelles (Cur-MSA) and Curcumin Loaded Solid Self-assembly Micelles (Cur-SMSA) 40
3.3.10 Pharmaceutical Formulations of Curcumin Loaded Solid Self-assembly Micelles (Cur-SMSA) 42
3.4 Discussions 43
3.5 Conclusion 49
Chapter 4: One-Pot Solidification of Micro-capsule Emulsifying Curcumin and the Application of Psoriasis Relieving 50
4.1 Introduction and Motivation 50
4.1.1 Psoriasis 50
4.1.2 Treatments for Psoriasis 52
4.1.3 Curcumin Relieved the Inflammatory Skin Lesion of Psoriasis 53
4.1.4 Opportunity and Possibility of Formulated Curcumin for Psoriasis Relieving 54
4.2 Experimental Design and Methods 55
4.2.1 Experimental Design 55
4.2.2 Preparation of Curcumin Loaded Micelles by Micro-capsule Emulsifying Process 56
4.2.3 Preparation of Solid Curcumin Loaded Micro-capsule Emulsifying Micelles by One Pot Solidification Process 56
4.2.4 Characterization of Micelles, Curcumin Loaded Micro-capsule Emulsifying Micelles (Cur-MMCE), and Solid Curcumin Loaded Micro-capsule Emulsifying Micelles (Cur-SMMCE) 56
4.2.5 Quantitative Analysis of Curcumin 57
4.2.6 Water Solubility Study 57
4.2.7 Imiquimid-induced Psoriasis Mice Model 58
4.2.8 Scoring the Skin Inflammation Severity 58
4.2.9 Histopathological and Immunohistochemical Analysis 59
4.2.10 Staining and Flow Cytometry Analysis 59
4.2.11 Statistical Analysis 60
4.3 Results 61
4.3.1 Characterization of Curcumin Loaded Micro-capsule Emulsifying Micelles (Cur-MMCE) and Solid Curcumin Loaded Micro-capsule Emulsifying Micelles (Cur-SMMCE) 61
4.3.2 Water Solubility Study of Curcumin Loaded Micro-capsule Emulsifying Micelles (Cur-MMCE) and Curcumin Loaded Solid Micro-capsule Emulsifying Micelles (Cur-SMMCE) 64
4.3.3 Psoriasis Relieving Efficacy of Curcumin-Loaded Solid Micro-capsule Emulsifying Micelles (Cur-SMMCE) in Imiquimod-induced Psoriasis-like Skin Lesions 66
4.3.4 Histological Analysis of Imiquimod-induced Psoriasis-like Skin Lesions with Hematoxylin and Eosin Staining 69
4.3.5 Immunohistochemical Analysis of Imiquimod-induced Psoriasis-like Skin Lesions with Ki67 Staining 71
4.3.6 Immunohistochemical Analysis of Imiquimod-induced Psoriasis-like Skin Lesions with CD3+ T Cell Staining 72
4.3.7 Immunohistochemical Analysis of Imiquimod-induced Psoriasis-like Skin Lesions with Ly6G/Gr1+ Neutrophil Staining 73
4.3.8 Curcumin-Loaded Micelles (Cur-SMMCE) Treatment without Reduction of the Percentage of IL-17/IL-22 Producing Splenic CD4+ and γδ T Cells in Imiquimod-induced Psoriasis Mice 75
4.4 Discussions 79
4.5 Conclusion 85
Reference 86

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