目前，大多數藥物輸送載體缺乏推動力，推動它們進入疾病部位進行有效載荷輸送。本文提出了一種電池驅動的核殼結構微米管給藥裝置，它由鋅（Zn）核和帶正電荷的聚(3,4-乙烯二氧噻吩) (PEDOT+) 的殼構成，其殼負載有陰離子模型藥物，這種核殼結構微米管在電解質溶液中由電偶作用形成“伽凡尼電池”。將這種鋅基伽凡尼電池浸入生理環境時，根據局部pH環境可自發發生兩組競爭的氧化還原反應。低pH下，H+ 還原產生氫氣占主導地位，產生的氫氣可推動Zn電池作為微型馬達產生運動；而在中性pH下，主要發生PEDOT+ 的還原，從而可以釋放負載的藥物。在小鼠中觀察表明，自供電的Zn電池可以在口服給藥後快速反應並在胃液中運動，顯著地提高了它們在粘液層中的滲透和保留以用於局部藥物釋放，類似於直接注射到皮下組織。組織實驗均未表現出任何顯著的炎症或細胞凋亡，這表明所開發的鋅-基電池具有作為安全的藥物遞送裝置的潛力。

Most drug delivery vehicles lack thrust that propels them to disease sites for payload delivery. Herein, a microrod comprising a zinc (Zn) core and a positively-charged poly(3,4-ethylenedioxythiophene) (PEDOT+) shell incorporating an anionic model drug, which form a “galvanic cell” in an electrolyte solution, is proposed as a battery-driven drug delivery device. Upon immersion of the proposed Zn-based batteries in a physiological environment, two sets of redox reactions that compete with each other in a manner determined by the local pH occur spontaneously. At low pH, the reduction of H+ to H2 bubbles, which are essential to propel the Zn batteries as micromotors, prevails, while at higher pH, the reduction of PEDOT+ to actuate galvanically payload release dominates. Observations in mice suggest that the self-powered Zn batteries may rapidly react and move in the gastric fluid after oral administration, considerably improving their penetration and retention in the mucus layer for localized drug release, similar to those directly injected into the subcutaneous tissue. None of the investigated tissues exhibited any significant inflammation or cell apoptosis, revealing that the developed Zn-based batteries have potential to serve as safe drug delivery devices.
 

ABSTRACT......................................................................................................................... i
TABLE OF CONTENT.................................................................................................... iii
LIST OF FIGURES............................................................................................................ vi
Chapter 1.......................................................................................................................... 1
Introduction .................................................................................................................... 1
1.1. Introduction of Smart Drug Delivery System (DDS)................................. 1
1.2. Stimuli for Drug Delivery..................................................................................... 1
1.3. Micro/Nanomotor- a New Class of DDSs..................................................... 2
1.4. Galvanic Battery...................................................................................................... 4
1.5. Drug Loading and Release Mechanism of Poly(3,4-ethylenedioxythiophene) (PEDOT).......................................................................... 4
1.6. Self-Powered Battery-Driven Drug Delivery Device................................. 5
Chapter 2........................................................................................................................... 9
Materials and Methods................................................................................................ 9
2.1. Materials.................................................................................................................... 9
2.2. Preparation of Zn/PEDOT+SRB− Microtubes............................................. 9
2.3. Characterization of Zn/PEDOT+SRB− Microtubes................................... 11
2.4. Mock Battery Assembly....................................................................................... 11
2.5. Electrochemical Measurements....................................................................... 12
2.6. Evolution of Gaseous H2..................................................................................... 12
2.7. Propulsion of Zn Microtubes............................................................................. 12
2.8. SRB− Stability.......................................................................................................... 13
2.9. SRB− Release Profiles.......................................................................................... 13
2.10. Animal Study......................................................................................................... 13
2.11. Penetration and Retention of the Zn Microtubes in the Gastric Mucus Layer and Their Localized Drug Releases.............................................................. 14
2.12. Potential in vivo toxicity of the Zn microtubes......................................... 15
2.13. Statistical analysis................................................................................................ 15
Chapter 3............................................................................................................................ 16
Results and Discussion.................................................................................................. 16
3.1. Characteristics of Zn Microtubes...................................................................... 16
3.2. Mock Battery............................................................................................................. 17
3.3. Electrochemical Analysis...................................................................................... 18
3.4. Evolution of gaseous H2....................................................................................... 20
3.5. SRB− Release Profiles............................................................................................ 21
3.6. Penetration and Retention of the Zn Microtubes in the Gastric Mucus Layer and Their Localized Drug Releases............................................................... 23
3.7. In Vivo toxicity.......................................................................................................... 25
Chapter 4............................................................................................................................ 27
Conclusion......................................................................................................................... 27
References......................................................................................................................... 28

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