透明质酸修饰的醇质体作为紫杉醇透皮给药的载体
发布时间：2023-05-10 19:45
紫杉醇(PTX)因其独特有效的抗肿瘤效果,在临床上被广泛用于多种肿瘤的化疗治疗,有研究表明它还对不同类型的非黑素瘤皮肤癌(如光化性角化病和紫外线辐射引起的恶性病变)的治疗也有着巨大的潜力。然而,PTX溶解度低,使得其口服生物利用度低,且其对正常细胞有毒副作用。据此,开发给药载体用于安全、高效递送PTX具有十分重要的意义。本文制备了一种负载/包封PTX的、透明质酸修饰的醇质体(HA-ES-PTX),以期通过透皮的方式给药治疗非黑素瘤皮肤癌。首先,本文制备了负载PTX的阳离子醇脂体(ES-PTX),再通过静电吸附的原理,将带有负电的透明质酸HA吸附到阳离子醇脂体(ES-PTX)的表面,从而制备出了透明质酸修饰的负载PTX的醇质体HA-ES-PTX。接着,表征了 HA-ES-PTX:(1)透射电子显微镜(TEM)显示,HA-ES-PTX显示出球形颗粒,平均大小为183.7±3.4nm;(2)动态光散射(DLS)显示,HA-ES-PTX带负电,Zeta电势为-18.6±0.9 mV;(3)通过离心分析,测得HA-ES-PTX封装效率为86±1.9%。然后,研究了 HA-ES-PTX的细胞摄取和...
【文章页数】：123 页
【学位级别】：硕士
【文章目录】：
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
本文编号：3813390
【文章页数】：123 页
【学位级别】：硕士
【文章目录】：
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
本文编号：3813390
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