紫杉醇(PTX)因其獨(dú)特有效的抗腫瘤效果,在臨床上被廣泛用于多種腫瘤的化療治療,有研究表明它還對(duì)不同類(lèi)型的非黑素瘤皮膚癌(如光化性角化病和紫外線輻射引起的惡性病變)的治療也有著巨大的潛力。然而,PTX溶解度低,使得其口服生物利用度低,且其對(duì)正常細(xì)胞有毒副作用。據(jù)此,開(kāi)發(fā)給藥載體用于安全、高效遞送PTX具有十分重要的意義。本文制備了一種負(fù)載/包封PTX的、透明質(zhì)酸修飾的醇質(zhì)體(HA-ES-PTX),以期通過(guò)透皮的方式給藥治療非黑素瘤皮膚癌。首先,本文制備了負(fù)載PTX的陽(yáng)離子醇脂體(ES-PTX),再通過(guò)靜電吸附的原理,將帶有負(fù)電的透明質(zhì)酸HA吸附到陽(yáng)離子醇脂體(ES-PTX)的表面,從而制備出了透明質(zhì)酸修飾的負(fù)載PTX的醇質(zhì)體HA-ES-PTX。接著,表征了 HA-ES-PTX:(1)透射電子顯微鏡(TEM)顯示,HA-ES-PTX顯示出球形顆粒,平均大小為183.7±3.4nm;(2)動(dòng)態(tài)光散射(DLS)顯示,HA-ES-PTX帶負(fù)電,Zeta電勢(shì)為-18.6±0.9 mV;(3)通過(guò)離心分析,測(cè)得HA-ES-PTX封裝效率為86±1.9%。然后,研究了 HA-ES-PTX的細(xì)胞攝取和...

【文章頁(yè)數(shù)】：123 頁(yè)

【學(xué)位級(jí)別】：碩士

【文章目錄】：
摘要
Abstract
Chapter 1. Introduction
    1.1 Overview of dissertation
    1.2 Structure of skin
    1.3 Advantages of TDDS
    1.4 Disadvantages of TDDS
    1.5 Basic components of TDDS
        1.5.1 Polymer matrix
        1.5.2 Drug
        1.5.3 Permeation enhancers
    1.6 Approaches used in the development of TDDS
        1.6.1 Membrane permeation controlled systems
        1.6.2 Adhesive dispersion type systems
        1.6.3 Matrix diffusion-controlled systems
        1.6.4 Micro-reservoir type or micro-sealed dissolution-controlled system
    1.7 Transdermal enhancement technologies
        1.7.1 Chemical enhancers
        1.7.2 Biological enhancers
        1.7.3 Micro-nanocarriers
        1.7.4 Physical enhancement devices
    1.8 Characterization of TDDS
        1.8.1 Particle Size and Zeta Potential
        1.8.2 Dynamic Light Scattering (DLS)
        1.8.3 Electron Microscopy
        1.8.4 X-ray diffraction or Differential Scanning Calorimetry (DSC)
        1.8.5 Atomic Force Microscopy AFM
        1.8.6 In-vitro Drug Permeation Studies
        1.8.7 Skin Irritation Test
Chapter 2. Ethosomes, Hyaluronic Acid & Paclitaxel
    2.1 Ethosomes
    2.2 Composition of ethosomes
    2.3 Ethosomes preparation methods
        2.3.1 Preparation by cold method
        2.3.2 Preparation by hot method
        2.3.3 Preparation by the classical method
        2.3.4 Lipid film hydration method
    2.4 Influence of high alcohol content
    2.5 Characterization of ethosomal system
        2.5.1 Morphology
        2.5.2 Particle size and size distribution
        2.5.3 Zeta potential
        2.5.4 Drug content
        2.5.5 Entrapment Efficiency
        2.5.6 Stability
        2.5.7 In vitro drug release study and Drug Deposition study
    2.6 Uniqueness of ethosomes
    2.7 Application of Ethosomes as a Carrier System
        2.7.1 Pilosebaceous targeting
        2.7.2 Transdermal delivery of hormones
        2.7.3 Delivery of anti-parkinsonism agent
        2.7.4 Transcellular delivery
        2.7.5 Topical delivery of DNA
        2.7.6 Delivery of anti-arthritis drug
        2.7.7 Phenylethyl resorcinol (PR) loaded ethosomes
        2.7.8 Aceclofenac loaded ethosomes
    2.8 Research trials of ethosomes with herbal compounds
    2.9 Research trials of ethosomes in cosmetics
    2.10 Hyaluronic Acid
    2.11 Occurrence
    2.12 Applications of Hyaluronic Acid
        2.12.1 Oncology
        2.12.2 HA as Transdermal drug delivery carrier
        2.12.3 Tumor targeting drug delivery and surface modification
    2.13 Background of Paclitaxel
    2.14 Chemical Structure
    2.15 Mechanism of Action
    2.16 Mechanism of Drug Resistance
    2.17 Pharmacokinetics
    2.18 Paclitaxel and the Immune System
    2.19 Clinical Studies
    2.20 Nanoparticle-Based Paclitaxel Delivery Systems
Chapter 3. Experimental Study
    3.1 Introduction
    3.2 Material and methods
        3.2.1 Materials
        3.2.2 Ethosomes preparation
    3.3 Characterization of ES-PTX and HA-ES-PTX
        3.3.1 Encapsulation efficiency
        3.3.2 Size and Zeta potential
        3.3.3 Morphology
    3.4 Analysis of intracellular uptake
    3.5 In vitro cytotoxicity
    3.6 In vitro skin permeation
    3.7 Calculation of fluxes
    3.8 Result and Discussion
        3.8.1 Physicochemical Characterization of HA-ES-PTX
        3.8.2 Encapsulation efficiency
        3.8.3 Morphology
        3.8.4 Intercellular uptake studies
        3.8.5 In vitro cytotoxicity
        3.8.6 In vitro skin permeation
Chapter 4. Conclusion and Future Work
    4.1 Summary
    4.2 Future Work
List of References
Acknowledgment
List of Publications



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