瘧疾是一種惡性寄生蟲病,通過瘧原蟲這一特殊種類的生物進(jìn)行傳播,其中惡性瘧原蟲（PF）是主要的傳播瘧疾的單細(xì)胞寄生蟲,而蚊子能夠?qū)F快速帶入血液,進(jìn)而感染肝細(xì)胞和血細(xì)胞。由于這種傳染性,致使人引發(fā)多種病癥甚至死亡。因此,瘧疾是一種嚴(yán)重的疾病。蒿甲醚,一種高效的抗瘧疾藥物,具有治愈感染P.F.患者的潛力。然而,它的治療功效和臨床應(yīng)用受其生物利用度差,半衰期短和快速降解等因素的限制。這些限制可以通過與天然生物增強(qiáng)劑如胡椒堿的組合來解決。本文中,我們通過將胡椒堿與聚乙二醇-共-羥基乙酸（PLGA）和基于殼聚糖的核-殼微粒包封在一起來克服蒿甲醚藥物的局限性。本研究使用同軸電噴霧（CES）系統(tǒng),該系統(tǒng)已被確立為開發(fā)核-殼微粒的有效策略,來制備微粒。通過優(yōu)化的工藝參數(shù),以高封裝效率（75.6%和78.8%）制備蒿甲醚-胡椒堿負(fù)載的PLGA-殼聚糖微粒（AP-PLGA-C5）和蒿甲醚-胡椒堿負(fù)載的PLGA微粒（AP-PLGA）,平均尺寸為2.2和1.7μm,其中載藥量（LE）分別9.7%和9.4%,且能夠持續(xù)釋放。此外,XRD和DSC結(jié)果表明,當(dāng)通過CES方法包封在微粒中時(shí),蒿甲醚和胡椒堿轉(zhuǎn)變?yōu)闊o定... 

【文章來源】：中國科學(xué)技術(shù)大學(xué)安徽省 211工程院校 985工程院校

【文章頁數(shù)】：114 頁

【學(xué)位級別】：碩士

【文章目錄】：
Abstract
摘要
Glossary of Abbreviations
Chapter 1. Introduction
    1.1 Malaria
    1.2 History
    1.3 Transmission and Life Cycle of Malaria
    1.4 Symptoms and Complications
    1.5 Malaria Diagnosis
        1.5.1 Clinical Diagnosis
        1.5.2 Laboratory Diagnosis
    1.6 Conventional Treatment for Malaria
    1.7 Nanomedicine Treatment for Malaria
    1.8 Artemisinin and its derivatives
        1.8.1 Artemether
        1.8.2 Chemistry and Structure of Artemether and Fast Facts
        1.8.3 Mechanism of Artemether Action
        1.8.4 Pharmacokinetics of Drug
        1.8.5 Recommended Dosage and Side Effects
        1.8.6 Artemether Interaction in Human Body
        1.8.7 Available Forms and Restrictions/Disadvantages
Chapter 2. Bioenhancer
    2.1 Introduction
    2.2 The concept of Bioavailability Enhancers
    2.3 History of Bioenhancers
    2.4 Piperine
        2.4.1 Properties of Piperine
        2.4.2 Antioxidant activity
        2.4.3 Bioenhancing Ability
    2.5 Advantages of Using Piperine as Bioenhancer
        2.5.1 Proposed Mechanism for Bio enhancing Effect
    2.6 Biodegradable Polymer
        2.6.1 Poly lactic-co-glycolic Acid (PLGA)
        2.6.2 Pharmacokinetic of PLGA
        2.6.3 Chitosan
        2.6.4 General properties of chitosan
Chapter 3. Electrospray System
    3.2 Introduction
    3.3 Principle of Electrospray
        3.3.1 Single Axial Electrospray
        3.3.2 Coaxial Electrospray System
    3.4 Electrospray Modes
    3.5 The Taylor Cone jet Mode Stability
    3.6 Process Parameters of Coaxial Electrospray System
    3.7 Effect of Applied Voltages on Stable Cone-Jet
    3.8 Effect of Flow Rates on Stable Cone jet
    3.9 Components of the Electrospray System
    3.10 Electrified Droplet Concept & Identification of Morphology
    3.11 Properties of Liquids
        3.11.1 Electrokinetics of Liquids
        3.11.2 Electrical Permittivity
        3.11.3 Interfacial Tension and Surface Tension
        3.11.4 Viscosity
        3.11.5 Liquid concentration
        3.11.6 Scaling law
Chapter 4. Experimental Study
    4.1 Introduction
    4.2 Materials and Methods
        4.2.1 Materials
        4.2.2 Experimental Setup
    4.3 Morphological characterization
        4.3.1 Morphology and Size Distribution Analysis
        4.3.2 Core-Shell Structured Evaluation
        4.3.3 Thermal Analysis
        4.3.4 Crystallinity using X-ray diffractometer
        4.3.5 UPLC Analysis
        4.3.6 Drug Encapsulation Efficiency (EE%)and Loading Rate (LR%)
        4.3.7 In Vitro Drug Release
        4.3.8 Cell Culture and Maintenance
        4.3.9 Evaluation of Cytotoxicity
    4.4 RESULTS AND DISCUSSION
        4.4.1 Fabrication of AP-PLGA and AP-PLGA-CS Microparticles
        4.4.2 Preparation of Inner and Outer solutions
        4.4.3 Characterization of AP-PC Microparticles and AP-P Microparticles
        4.4.4 Core-shell structure formation and verification of AP-PLGA and AP-PLGA-CSMicroparticles
        4.4.5 XRD Analysis of AP-PC and AP-P Microparticles
        4.4.6 DSC measurements on AP-PLGA and AP-PLGA-CS microparticles
        4.4.7 Encapsulation Efficiency and Cytotoxicity
        4.4.8 In Vitro Release profile of AP-PLGA and AP-PLGA-CS Microparticles
Chapter 5. Conclusion and Future Work
    5.1 Summary
List of References
Acknowledgements


【參考文獻(xiàn)】：
期刊論文
[1]胡椒堿抗實(shí)驗(yàn)性胃潰瘍的作用(英文)[J]. 白音夫,旭紅.  Acta Pharmacologica Sinica. 2000(04)
[2]THE INFECTIVITY OF GAMETOCYTES OF PLASMODIUM FALCIPARUM FROM PATIENTS TREATED WITH ARTEMISININ[J]. 陳沛泉,李國橋,郭興伯,何坤榮,符永新,符林春,宋玉宗.  Chinese Medical Journal. 1994(09)



本文編號：3375762