아주대학교

목차

1. Introduction 2
1.1. Alzheimer's disease 2
1.2. Drugs and mechanisms of action for the treatment of Alzheimer's disease 3
1.3. Drug delivery system and limitations for the treatment of Alzheimer's disease 4
1.4. Controlled release drug delivery system for the treatment of Alzheimer's disease 10
1.5. Thermoresponsive hydrogels 12
1.6. Microspheres 15
1.7. Manufacturing method of microsphere 16
1.8. Purpose and strategy of this works 18
2. Materials and method 24
2.1. Materials 24
2.2. Preparation of donepezil-loaded microsphere using monoaxial one-nozzle ultrasonic atomizer 25
2.3. Characterization and morphology evaluation of donepezil-loaded microspheres 26
2.4. Encapsulation efficiency of donepezil-loaded microspheres 27
2.5. Particle size measurement and stability test of donepezil-loaded microsphere 28
2.6. Mechanical properties of donepezil-loaded microsphere 29
2.7. Synthesis and characterization of PCL 29
2.8. Preparation and rheological characterization donepezil-loaded combination formulations 31
2.9. Uniformity evaluation of donepezil-loaded combination formulations during injection 32
2.10. Injectability and injection force evaluation of donepezil-loaded combination formulation 33
2.11. In vitro drug release of donepezil-loaded combination formulation 34
2.12. In vivo subcutaneous injection of donepezil-loaded combination formulation 35
2.13. In vivo drug release of donepezil-loaded combination formulation 37
2.14. In vivo biodegradation evaluation of donepezil-loaded combination formulation 38
2.15. In vivo physicochemical evaluation of donepezil-loaded combination formulation 39
2.16. In vivo biocompatibility evaluation of donepezil-loaded combination formulation 40
2.17. Statistical analyses 42
3. Result and discussion 43
3.1. Preparation and characterization of donepezil-loaded microsphere 43
3.2. Encapsulation and yield of donepezil-loaded microsphere 46
3.3. Comparison of particle size and distribution of donepezil-loaded microspheres 49
3.4. Stability evaluation of donepezil-loaded microsphere 53
3.5. Mechanical property of donepezil-loaded microsphere 55
3.6. Preparation and rheological characterization donepezil-loaded combination formulations 58
3.7. Uniformity evaluation of donepezil-loaded combination formulations during injection 64
3.8. Injectability and injection force evaluation of donepezil-loaded combination formulations 68
3.9. In vitro drug release of donepezil-loaded combination formulations 74
3.10. In vivo subcutaneous injection of donepezil-loaded combination formulations 78
3.11. In vivo drug release of donepezil-loaded combination formulations 86
3.12. In vivo biodegradation and morphology evaluation of donepezil-loaded combination formulations 95
3.13. In vivo biodegradation and physicochemical evaluation of donepezil-loaded combination formulations 101
3.14. In vivo biocompatibility evaluation of donepezil-loaded combination formulations 111
4. Conclusion 122
5. References 124