簡易檢索 / 詳目顯示

研究生: 陳俊翰
Chun-han Chen
論文名稱: 逐層組裝聚電解質於聚丙烯腈靜電紡絲表面及藥物釋放與抗生物沾黏特性之應用
Electrospun Polyacrylonitrile Nanofibers Modified with Polyelectrolyte by Layer-by-Layer for Drug Release and Anti-biofouling Properties
指導教授: 陳建光
Jem-kun Chen
口試委員: 邱顯堂
Hsien-tang Chiu
楊銘乾
Ming-chien Yang
蘇清淵
Ching-iuan Su
學位類別: 碩士
Master
系所名稱: 工程學院 - 材料科學與工程系
Department of Materials Science and Engineering
論文出版年: 2013
畢業學年度: 101
語文別: 中文
論文頁數: 87
中文關鍵詞: 靜電紡絲逐層組裝聚電解質聚丙烯腈藥物控釋抗生物沾黏
外文關鍵詞: Layer-by-Layer
相關次數: 點閱:238下載:0
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

本研究以靜電紡絲技術製備聚丙烯腈高分子(Polyacrylonitrile, PAN)奈米纖維,先透過氫氧化鈉將奈米纖維表面鹼催化改質使具有羧酸官能基(-COOH),再利用逐層組裝技術(Layer-by-Layer)將兩種不同電性之聚電解質:聚丙烯氯化銨(Poly(allylamine hydrochlorid, PAH)和聚丙烯酸(Poly(acrylic acid), PAA)交互沉積至奈米纖維表面。
本研究利用不同電性之模式藥物,正電性的亞甲基藍(Methylene blue ,MB)及負電性的肝素(Heparin)隨著聚電解質裝載至奈米纖維表面,並透過藥物裝載-釋放實驗(Drug Loading-Release)評估奈米纖維於藥物傳遞之應用潛力,且可藉由調整環境pH值達到藥物控釋之功能。
此外,利用雷射共軛焦顯微鏡(Laser Scanning Confocal Microscope, LSCM)觀察Fluorescein (FITC)-conjugated AffiniPure Goat Anti-Rabbit IgG抗體對於逐層組裝聚電解質奈米纖維之抗沾黏程度,發現聚電解質奈米纖維抗體不利沾黏於奈米纖維上,展現出抗生物沾黏(Anti-biofouling)之特性。


In this work, Polyacrylonitrile (PAN) nanofiber were fabricated by using the electrospinning technique, and the surface was modified with carboxylic acid groups. We deposit two oppositely charged polyelectrolytes: poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) bilayers on the PAN nanofiber by Layer-by-Layer technology.
Furthermore we used two oppositely charged drug: methylene blue (MB) and heparin. These two kinds of drugs were used as the model drug to evaluate the potential application of the nanofibers for drug delivery. The release of MB and heparin was controlled in a phosphate buffered saline (PBS) solution by changing the pH of the solution. The controlled release of drugs from electrospinning nanofibers have potential applications as drug carriers in biomedical science.
In addition, laser scanning confocal microscope (LSCM) measurements were included to determine the relative amount of antibody that adsorbed to these polyelectrolyte nanofibers to examine the property of anti-biofouling.
These polyelectrolyte fibers, due to their simple fabrication and the controlled release property, can be used for drug delivery devices and in other potential application.

摘要 III Abstract IV 致謝 V 目錄 VI 表目錄 IX 圖目錄 X 第1章 前言 1 1.1 研究背景 1 1.2 研究動機與目的 2 第2章 理論與文獻回顧 3 2.1 靜電紡絲工程 3 2.1.1 靜電紡絲原理 4 2.1.2 靜電紡絲裝置 5 2.1.3 靜電紡絲參數 6 2.2 奈米纖維在組織工程及藥物傳遞之應用 7 2.3 藥物控制釋放 10 2.3.1 藥物控制釋放系統 10 2.3.2 藥物控制釋放分類 11 2.4 聚電解質多層膜 17 2.5 抗生物沾黏材料簡介 20 2.6 肝素 23 2.7 比爾─朗伯定律 25 第3章 儀器原理 27 3.1 高解析度場發射掃描式電子顯微鏡 27 3.2 紫外光-可見光光譜儀 28 3.3 光激發螢光光譜儀 29 3.4 雷射掃描式共軛焦顯微鏡 30 第4章 實驗流程與方法 32 4.1 實驗流程圖 32 4.2 實驗藥品 33 4.3 實驗儀器 35 4.4 實驗步驟 37 4.4.1 靜電紡絲纖維製備 37 4.4.2 鹼催化靜電紡絲纖維改質 38 4.4.3 逐層組裝聚電解質多層膜 39 4.4.4 磷酸緩衝溶液配製 41 4.4.5 靜電紡絲纖維藥物裝載 42 4.4.6 亞甲基藍標準曲線 43 4.4.7 肝素標準曲線 43 4.4.8 靜電紡絲纖維藥物體外釋放實驗 45 4.4.9 靜電紡絲纖維抗生物沾黏實驗 46 第5章 結果與討論 47 5.1 奈米纖維特性分析 47 5.1.1 靜電紡絲溶液濃度探討 47 5.1.2 鹼催化PAN紡絲纖維改質 51 5.2 逐層組裝聚電解質多層膜表面形貌分析 54 5.2.1 FE-SEM表面形貌分析 54 5.2.2 FTIR官能基鑑定 64 5.3 藥物裝載-釋放之探討 65 5.3.1 亞甲基藍裝載-釋放 65 5.3.2 肝素裝載-釋放 70 5.4 抗生物沾黏特性 75 5.4.1 FITC之光譜分析 75 5.4.2 雷射共軛焦顯微鏡形態分析 76 第6章 結論 82 參考文獻 83

1. Fu, G. D.; Xu, L. Q.; Yao, F.; Zhang, K.; Wang, X. F.; Zhu, M. F.; Nie, S. Z., Smart nanofibers from combined living radical polymerization, "click chemistry", and electrospinning. ACS Appl Mater Interfaces 2009, 1, (2), 239-43.
2. Huang, Z.-M.; Zhang, Y. Z.; Kotaki, M.; Ramakrishna, S., A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Composites Science and Technology 2003, 63, (15), 2223-2253.
3. Ozcam, A. E.; Roskov, K. E.; Genzer, J.; Spontak, R. J., Responsive PET nano/microfibers via surface-initiated polymerization. ACS Appl Mater Interfaces 2012, 4, (1), 59-64.
4. Heikkila, P., Electrospinning of polyacrylonitrile (PAN) solution: Effect of conductive additive and filler on the process. eXPRESS Polymer Letters 2009, 3, (7), 437-445.
5. Yoo, H. S.; Kim, T. G.; Park, T. G., Surface-functionalized electrospun nanofibers for tissue engineering and drug delivery. Advanced drug delivery reviews 2009, 61, (12), 1033-42.
6. Shunkevich, A. A.; Akulich, Z. I.; Mediak, G. V.; Soldatov, V. S., Acid–base properties of ion exchangers. III. Anion exchangers on the basis of polyacrylonitrile fiber. Reactive and Functional Polymers 2005, 63, (1), 27-34.
7. Wang, Z.-G.; Wan, L.-S.; Xu, Z.-K., Surface engineerings of polyacrylonitrile-based asymmetric membranes towards biomedical applications: An overview. Journal of Membrane Science 2007, 304, (1-2), 8-23.
8. Reneker, D. H.; Chun, I., Nanometre diameter fibres of polymer, produced by electrospinning. Nanotechnology 1996, 7, 216-223.
9. Taylor, G., Disintegration of Water Drops in an Electric Field. Proc. R. Soc. Lond. 1964, 280, 383-397.
10. Reznik, S. N.; Yarin, A. L.; Theron, A.; Zussman, E., Transient and steady shapes of droplets attached to a surface in a strong electric field. Journal of Fluid Mechanics 2004, 516, 349-377.
11. Fridrikh, S.; Yu, J.; Brenner, M.; Rutledge, G., Controlling the Fiber Diameter during Electrospinning. Physical Review Letters 2003, 90, (14).
12. Shin, Y. M.; Hohman, M. M.; Brenner, M. P.; Rutledge, G. C., Experimental characterization of electrospinning- the electrically forced jet and instabilities. Polymer 2001, 42, 9955-9967.
13. Doshi, J.; Reneker, D. H., Electrospinning process and applications of electrospun fibers. Journ of Electrostatics 1995, 35, 151-160.
14. Bhardwaj, N.; Kundu, S. C., Electrospinning: a fascinating fiber fabrication technique. Biotechnology advances 2010, 28, (3), 325-47.
15. Tan, S. H.; Inai, R.; Kotaki, M.; Ramakrishna, S., Systematic parameter study for ultra-fine fiber fabrication via electrospinning process. Polymer 2005, 46, (16), 6128-6134.
16. Pillay, V.; Dott, C.; Choonara, Y. E.; Tyagi, C.; Tomar, L.; Kumar, P.; du Toit, L. C.; Ndesendo, V. M. K., A Review of the Effect of Processing Variables on the Fabrication of Electrospun Nanofibers for Drug Delivery Applications. Journal of Nanomaterials 2013, 2013, 1-22.
17. R., B., Controlled release of biologically active agents. Wiley: Canda, 1987.
18. Banerjee, P. S.; Robinson, J. R., Novel Drug Delivery Systems. Clinical Pharmacokinetics 1991, 20, (1), 1-14.
19. H, L.; M, A.; M, L., Oral absorption and disposition of isosorbide dinitrate and isosorbide mononitrates in man. Arzneimittel-Forschung 1983, 33, (7), 980-984.
20. Duchin, K. L.; McKinstry, D. N.; Cohen, A. I.; Migdalof, B. H., Pharmacokinetics of Captopril in Healthy Subjects and in Patients with Cardiovascular Diseases. Clinical Pharmacokinetics 1988, 14, (4), 241-259.
21. Rudolph, F. B., Diffusion in a multicomponent inhomogeneous system with moving boundaries. I. Swelling at constant volume. Journal of Polymer Science: Polymer Physics Edition 1979, 17, (10), 1709-1718.
22. Rudolph, F. B., Diffusion in a multicomponent inhomogeneous multiphase system with moving boundaries. II. Increasing or decreasing volume (swelling or drying). Journal of Polymer Science: Polymer Physics Edition 1980, 18, (12), 2323-2336.
23. Hsieh, D. S. T.; Rhine, W. D.; Langer, R., Zero-order controlled-release polymer matrices for micro- and macromolecules. Journal of Pharmaceutical Sciences 1983, 72, (1), 17-22.
24. Jarrott, B.; Drummer, O.; Hooper, R.; Anderson, A. I. E.; Miach, P. J.; Louis, W. J., Pharmacokinetic properties of captopril after acute and chronic administration to hypertensive subject. The American Journal of Cardiology 1982, 49, (6), 1547-1549.
25. Yoo, D.; Shiratori, S. S.; Rubner, M. F., Controlling Bilayer Composition and Surface Wettability of Sequentially Adsorbed Multilayers of Weak Polyelectrolytes. Macromolecules 1998, 31, 4309-4318.
26. Mendelsohn, J. D.; Barrett, C. J.; Chan, V. V.; Pal, A. J.; Mayes, A. M.; Rubner, M. F., Fabrication of Microporous Thin Films from Polyelectrolyte Multilayers. Langmuir 2000, 16, 5017-5023.
27. Shiratori, S. S.; Rubner, M. F., pH-Dependent Thickness Behavior of Sequentially Adsorbed Layers of Weak Polyelectrolytes. Macromolecules 2000, 33, 4213-4219.
28. Mendelsohn, J. D.; Yang, S. Y.; Hiller, J. A.; Hochbaum, A. I.; Rubner, M. F., Rational Design of Cytophilic and Cytophobic Polyelectrolyte Multilayer Thin Films. Biomacromolecules 2003, 4, 96-106.
29. Decher, G.; Schlenoff, J. B., Multilayer Thin Film. Weiley, 2003.
30. Lichter, J. A.; Van Vliet, K. J.; Rubner, M. F., Design of Antibacterial Surfaces and Interfaces: Polyelectrolyte Multilayers as a Multifunctional Platform. Macromolecules 2009, 42, (22), 8573-8586.
31. Zhao, Y.-H.; Zhu, X.-Y.; Wee, K.-H.; Bai, R., Achieving Highly Effective Non-biofouling Performance for Polypropylene Membranes Modified by UV-Induced Surface Graft Polymerization of Two Oppositely Charged Monomers. The Journal of Physical Chemistry B 2010, 114, 2422-2429.
32. Ostuni, E.; Chapman, R. G.; Holmlin, R. E.; Takayama, S.; Whitesides, G. M., A Survey of Structure-Property Relationships of Surfaces that Resist the Adsorption of Protein. Langmuir 2001, 17, 5605-5620.
33. Chang, Y.; Liao, S.-C.; Higuchi, A.; Ruaan, R.-C.; Chu, C.-W.; Chen, W.-Y., A Highly Stable Nonbiofouling Surface with Well-Packed Grafted Zwitterionic Polysulfobetaine for Plasma Protein Repulsion. Langmuir 2008, 24, 5453-5458.
34. Krishnan, S.; Weinman, C. J.; Ober, C. K., Advances in polymers for anti-biofouling surfaces. Journal of Materials Chemistry 2008, 18, (29), 3405.
35. Wang, H.-m.; Loganathan, D.; Linhardt, R. J., Determination of the pKa of glucuronic acid and the carboxy groups of heparin by 13C-nuclear-magnetic-resonance spectroscopy. Biochem. J. 1991, 278, 689-695.
36. Capila, I.; Linhardt, R. J., Heparin-Protein Interactions. Angewandte Chemie International Edition 2002, 41, (3), 390-412.
37. Hirsh, J.; Anand, S. S.; Halperin, J. L.; Fuster, V., Guide to Anticoagulant Therapy: Heparin : A Statement for Healthcare Professionals From the American Heart Association. Circulation 2001, 103, (24), 2994-3018.
38. 柯以侃, 儀器分析. 新文京: 2007.
39. Chiu, H. T., Fabrication of electrospun polyacrylonitrile ion-exchange membranes for application in lysozyme adsorption. Express Polymer Letters 2011, 5, (4), 308-317.
40. 翁漢昇, 幾丁聚醣包覆肝素之奈米微粒做為口服途徑傳遞肝素之可行性評估. 2007.
41. Smith, P. K.; Mallia, A. K.; Hermanson, G. T., Colorimetric method for the assay of heparin content in immobilized heparin preparations. Analytical Biochemistry 1980, 109, (2), 466-473.
42. Huang, Y.; Yu, H.; Xiao, C., pH-sensitive cationic guar gum/poly (acrylic acid) polyelectrolyte hydrogels: Swelling and in vitro drug release. Carbohydrate Polymers 2007, 69, (4), 774-783.
43. Kao, T.-H.; Chen, J.-K.; Cheng, C.-C.; Su, C.-I.; Chang, F.-C., Low-surface-free-energy polybenzoxazine/polyacrylonitrile fibers for biononfouling membrane. Polymer 2013, 54, (1), 258-268.
44. Chunder, A.; Sarkar, S.; Yu, Y.; Zhai, L., Fabrication of ultrathin polyelectrolyte fibers and their controlled release properties. Colloids and surfaces. B, Biointerfaces 2007, 58, (2), 172-9.
45. Choi, J.; Rubner, M. F., Influence of the Degree of Ionization on Weak Polyelectrolyte Multilayer Assembly. Macromolecules 2005, 38, 116-124.

無法下載圖示 全文公開日期 2018/07/26 (校內網路)
全文公開日期 本全文未授權公開 (校外網路)
全文公開日期 本全文未授權公開 (國家圖書館:臺灣博碩士論文系統)
QR CODE