| ABSTRACT | 第5-6页 |
| 摘要 | 第7-17页 |
| Chapter 1 General Introduction | 第17-33页 |
| 1.1 Current status of lung cancer | 第17-19页 |
| 1.2 Introduction of pulmonary delivery treatment | 第19-21页 |
| 1.3 Drug carriers for pulmonary inhalation treatment | 第21-27页 |
| 1.3.1 Nanoscale carriers for pulmonary inhalation treatment | 第25-26页 |
| 1.3.2 Micron level carriers for pulmonary inhalation treatment | 第26-27页 |
| 1.4 Combination therapy against lung cancer | 第27-30页 |
| 1.4.1 Drug combination in lung cancer therapy | 第28页 |
| 1.4.2 Drug and gene combination in lung cancer therapy | 第28-30页 |
| 1.5 Research topics | 第30-33页 |
| Chapter 2 Development of biodegradable polymeric microspheres | 第33-51页 |
| 2.1 Introduction | 第33-34页 |
| 2.2 Materials and methods | 第34-41页 |
| 2.2.1 Materials | 第34-35页 |
| 2.2.2 Synthesis route of poly(d,l-lactic-co-glycolic acid) (PLGA) | 第35页 |
| 2.2.3 Synthesis route of poly(γ-benzyl-L-glutamate) (PBLG) | 第35-36页 |
| 2.2.4 Characterization of PLGA and PBLG | 第36-37页 |
| 2.2.5 PLGA solid microspheres | 第37页 |
| 2.2.6 Porous PLGA microspheres | 第37-38页 |
| 2.2.7 Acid-sensitive PLGA microspheres | 第38页 |
| 2.2.8 PBLG microspheres | 第38-39页 |
| 2.2.9 Characterization of the microspheres | 第39页 |
| 2.2.10 Drug loading and drug release of the microspheres | 第39-40页 |
| 2.2.11 Cell experiments | 第40-41页 |
| 2.3 Results and Discussion | 第41-48页 |
| 2.3.1 Characterization of PLGA and PBLG | 第41-43页 |
| 2.3.2 Surface morphology of the microspheres | 第43-46页 |
| 2.3.3 Drug loading and drug release profile of the microspheres | 第46-48页 |
| 2.3.4 In vitro anti-tumor efficiency against lung cancer cell lines | 第48页 |
| 2.4 Conclusion | 第48-51页 |
| Chapter 3 Doxorubicin-loaded PLGA microspheres with wrinkledsurface and internal pores for long-acting release in pulmonary inhalationtreatment | 第51-63页 |
| 3.1 Introduction | 第51-52页 |
| 3.2 Materials and methods | 第52-56页 |
| 3.2.1 Materials and devices | 第52-53页 |
| 3.2.2 Preparation and characterization of the microspheres | 第53页 |
| 3.2.3 Drug loading and drug release | 第53-54页 |
| 3.2.4 In vitro cytotoxicity assays | 第54页 |
| 3.2.5 Animals and establishment of the tumor model | 第54页 |
| 3.2.6 Lung deposition of the microspheres | 第54-55页 |
| 3.2.7 In vivo antitumor efficiency | 第55-56页 |
| 3.3 Results and Discussion | 第56-62页 |
| 3.3.1 Characterization of PLGA microspheres | 第56-57页 |
| 3.3.2 Drug loading and drug release | 第57-58页 |
| 3.3.3 In vitro cytotoxicity assays | 第58-59页 |
| 3.3.4 Lung deposition experiment | 第59页 |
| 3.3.5 In vivo anti-tumor efficacy | 第59-61页 |
| 3.3.6 Histopathology study | 第61-62页 |
| 3.3.7 Survival rate | 第62页 |
| 3.4 Conclusion | 第62-63页 |
| Chapter 4 Synergistic co-delivery of doxorubicin and paclitaxel byporous PLGA microspheres for pulmonary inhalation treatment | 第63-77页 |
| 4.1 Introduction | 第63-64页 |
| 4.2 Materials and methods | 第64-67页 |
| 4.2.1 Materials | 第64页 |
| 4.2.2 Preparation of PLGA microspheres loaded with DOX/PTX | 第64-65页 |
| 4.2.3 Characterization of the drug loaded PLGA microspheres | 第65页 |
| 4.2.4 MTT assay | 第65页 |
| 4.2.5 In Vitro drug release | 第65-66页 |
| 4.2.6 Animal work | 第66-67页 |
| 4.2.7 Data analyzed | 第67页 |
| 4.3 Results and Discussion | 第67-75页 |
| 4.3.1 Combinational effects of DOX and PTX in the free form | 第67-69页 |
| 4.3.2 Porous PLGA microspheres | 第69-70页 |
| 4.3.3 Drug loading efficiency and drug loading content | 第70-71页 |
| 4.3.4 In vitro drug release of MS-DP(5/1)and MS-DP(2/1) | 第71页 |
| 4.3.5 Combinational effects of DOX and PTX in the PLGA microspheres | 第71-73页 |
| 4.3.6 Anti-tumor effects of drug loaded porous PLGA microspheres | 第73-74页 |
| 4.3.7 Histological examination | 第74-75页 |
| 4.4 Conclusion | 第75-77页 |
| Chapter 5 Appendix:PEGylated poly(aspartate-g-OEI)copolymers foreffective and prolonged gene transfection | 第77-93页 |
| 5.1 Introduction | 第77-78页 |
| 5.2 Materials and methods | 第78-82页 |
| 5.2.1 Materials | 第78-79页 |
| 5.2.2 Synthesis route of polymers | 第79页 |
| 5.2.3 Polymer characterization | 第79-80页 |
| 5.2.4 Measurement of particle size and zeta potential | 第80页 |
| 5.2.5 Gel retardation assay | 第80页 |
| 5.2.6 Cell experiments | 第80页 |
| 5.2.7 In vitro transfection | 第80-81页 |
| 5.2.8 BSA adsorption | 第81页 |
| 5.2.9 Cellular Uptake | 第81-82页 |
| 5.2.10 Animal work | 第82页 |
| 5.3 Results and Discussion | 第82-91页 |
| 5.3.1 Synthesis and characterization of the R-PAsp-g-OEI copolymers | 第82-85页 |
| 5.3.2 Particle size and Zeta potential analysis | 第85-86页 |
| 5.3.3 Agarose gel electrophoresis experiments | 第86-87页 |
| 5.3.4 In vitro toxicity | 第87页 |
| 5.3.5 Transfection assay | 第87-88页 |
| 5.3.6 BSA adsorption | 第88-89页 |
| 5.3.7 Intracellular uptake | 第89-90页 |
| 5.3.8 In vivo distribution | 第90-91页 |
| 5.4 Conclusion | 第91-93页 |
| REFERENCES | 第93-115页 |
| 附录 | 第115-127页 |
| ACKNOWLEDGEMENTS | 第127-129页 |
| 致谢 | 第129-131页 |
| 在读期间发表的学术论文与取得的其他研究成果 | 第131-132页 |
