簡易檢索 / 詳目顯示

回結果列表
研究生： 鄭偉志
Cheng, Wei-Chih
論文名稱： 聚丙烯酸-聚(2-乙基-2-噁唑啉)分子間複合物與十二烷基硫酸鈉之交互作用與作為藥物載體之應用
Poly(acrylic acid)-Poly(2-ethyl-2-oxazoline) Interpolymer Complexes:Interaction with Sodium Dodecyl Sulfate and Application in Drug Carrier
指導教授： 侯聖澍
Hou, Sheng-Shu
學位類別： 碩士
Master
系所名稱： 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年： 2015
畢業學年度： 103
語文別： 中文
論文頁數： 87
中文關鍵詞： 聚丙烯酸 、聚(2-乙基-2-噁唑啉) 、十二烷基硫酸鈉 、高分子間複合物
外文關鍵詞： Poly(acrylic acid), Poly(2-ethyl-2-oxazoline), sodium dodecyl sulfate, Interpolymer complexes, Drug carrier
相關次數： 點閱：81  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

    • 聚丙烯酸[poly(acrylic acid)，PAA]與非離子型高分子聚(2-乙基-2-噁唑啉)[poly(2-ethyl-2-oxazoline)，PEtOz]在水溶液中能藉由氫鍵作用力形成具有pH敏感性質的分子間複合物，而此般聚羧酸-非離子型高分子複合物由於具有作為藥物載體之潛力而在近年被廣泛研究。在此篇研究中，具有疏水性質的抗癌藥物阿黴素(doxorubicin，DOX)被導入PAA-PEtOz水溶液中以了解隨著高分子複合物生成而產生的疏水區域對疏水藥物的承載和相容效果；陰離子型界面活性劑十二烷基硫酸鈉(sodium dodecyl sulfate，SDS)也被添加至PAA-PEtOz水溶液中，藉此模擬生物系統中兩性分子對高分子複合物構型的影響。
    根據溶液穿透度及pyrene螢光光譜的觀測結果，SDS類微胞叢集所造成的靜電排斥力和立體障礙會與PAA及PEtOz之間的作用力產生競合關係；當SDS類微胞叢集吸附在PAA-PEtOz複合物上時，類微胞叢集造成的立體障礙及彼此之間的靜電排斥力將會導致複合物的分解；而SDS類微胞叢集率先吸附在PEtOz高分子鏈上時，類微胞叢集造成的立體障礙及靜電排斥力則會妨礙PEtOz與PAA的複合行為，除了複合物必須在較低的pH環境下藉由更強烈的氫鍵作用力才能生成外，PAA-PEtOz複合物的構型亦會變得較為鬆散。
    此外，PAA-PEtOz複合物對高分子濃度及溶液酸鹼度都相當的敏感，複合物的構型、緊密程度及疏水性質均會隨著溶液酸鹼度及高分子濃度而改變，而PAA-PEtOz複合物的疏水性質則會影響複合物對疏水藥物DOX的承載效果。在複合物的尺寸由於乘載DOX而增大並產生析出現象之前，DOX的承載效果將隨著複合物的疏水性質提升而優化；至於乘載於複合物疏水區域中的DOX的釋放行為方面，當複合物的疏水性質隨著環境pH值下降而提升時，DOX亦會有較為緩慢的釋放速率。

    In this study, polymer concentration and the pH of polymer solution was shown to have significant effect on the interaction between poly(acrylic acid) (PAA) and poly(2-ethyl-2-ozazoline) (PEtOz) and also on the structure of the interpolymer complexes (IPCs). In addition, Sodium dodecyl sulfate (SDS) was introduced into PAA/PEtOz solution so as to mimic the the microstructure change of interpolymer complexes caused by amphipiles in biological system. The competitive behavior between IPCs and SDS were studied in terms of pyrene solubilization and transparency. The microstructure of PAA-PEtOz IPCs was found to be varied with the amount of SDS added.
    Futhermore, doxorubicin (DOX) was added to PAA/PEtOz solution in order to examine the drug-loading capacity of PAA-PEtOz IPCs. It was found that the hydrophobicity of PAA-PEtOz IPCs dominated the loading efficiency of DOX before IPCs forming precipitate due to the growth of size by the solubiliztion of DOX. Moreover, the release rate of DOX from PAA-PEtOz IPCs was also found to be depended on the hydrophobicity of IPCs.

    摘要 I Extend abstract II 誌謝 VIII 總目錄 IX 表目錄 XIII 圖目錄 XIV 第一章 、緒論 1 1-1引言 1 1-2研究動機和目的 1 第二章 、文獻回顧 4 2-1界面活性劑 4 2-1-1微胞理論 4 2-2高分子/界面活性劑系統 7 2-2-1非離子型高分子/界面活性劑系統 7 2-2-2聚羧酸(陰離子型高分子)/界面活性劑系統 11 2-3聚羧酸/非離子型高分子交互作用 13 2-4聚羧酸/非離子型高分子/界面活性劑混合水溶液 16 2-5奈米藥物載體 17 2-5-1 EPR effect 18 2-5-2高分子間複合物於奈米藥物載體上之應用 19 第三章 、實驗原理 24 3-1酸鹼度測量儀的基本原理 24 3-1-1直接電位法 24 3-1-2溶液的酸鹼性 25 3-2分光光度計的基本原理 26 3-2-1穿透度與吸收度的測量 26 3-2-2比耳定律(Beer-Lambert Law) 26 3-3螢光光譜儀的基本原理 27 3-3-1螢光探針pyrene的應用 27 3-4穿透式電子顯微鏡(TEM)的基本原理 29 3-5紫外/可見光光譜儀的基本原理 29 3-6毛細管黏度計的基本原理 30 3-6-1 Hagen-Poiseuille equation 30 3-6-3本質黏度[η] (intrinsic viscosity) 31 3-6-4臨界交疊濃度c* 32 第四章 、實驗系統 33 4-1實驗藥品及儀器設備 33 4-1-1實驗藥品 33 4-1-2實驗器材 34 4-1-3分析儀器 34 4-2實驗製備方法 36 4-2-1界面活性劑Sodium dodecyl sulfate(SDS)的純化 36 4-2-2螢光探針pyrene的純化 37 4-2-3螢光探針法樣品之製備 37 4-2-4穿透度樣品之製備 40 4-2-5酸鹼度樣品之製備 40 4-2-6穿透式電子顯微鏡(TEM)樣品之製備 40 4-2-7藥物載體樣品製備 40 4-2-8藥物釋放實驗 42 4-2-9黏度樣品之製備 42 第五章 、結果與討論 43 5-1水溶液酸鹼環境對PEtOz/SDS雙成分系統交互作用之影響 43 5-1-1利用螢光光譜分析PEtOz/SDS雙成分系統之交互作用與水溶液酸鹼度之關係 44 5-1-2高分子之濃度效應於PEtOz/SDS雙成分系統之交互作用的影響 47 5-2水溶液中酸鹼環境對等當量比PAA/PEtOz複合物之影響 48 5-2-1以螢光光譜及穿透度分析水溶液酸鹼度於PAA/PEtOz複合物構型及複合機制之影響 48 5-2-2以動態光散射(DLS)分析水溶液酸鹼度於PAA/PEtOz複合物構型及尺寸分布之影響 53 5-2-3高分子之濃度效應於等當量比PAA/PEtOz複合物構型與複合機制之影響 55 5-3界面活性劑SDS對PAA/PEtOz複合物構型之影響 58 5-3-1以螢光光譜儀及穿透度計分析SDS濃度於PAA/PEtOz複合物構型之影響 59 5-3-2以穿透式電子顯微鏡(TEM)分析SDS濃度於PAA/PEtOz複合物構型之影響 62 5-3-3以動態光散射(DLS)分析SDS濃度於PAA/PEtOz複合物構型及尺寸分布之影響 64 5-3-4以螢光光譜儀及穿透度計分析SDS濃度於PAA/PEtOz複合物生成機制之影響 66 5-4 PAA/PEtOz複合物作為藥物載體之應用 74 5-4-1高分子濃度及水溶液酸鹼度於PAA/PEtOz等當量比複合物進行藥物乘載效果之影響 74 5-4-2環境酸鹼度於PAA/PEtOz複合物作為藥物載體之釋放速率的影響 78 第六章 、結論 81 參考文獻 82

    [1] Z. S. Nurkeeva, G. A. Mun, V. V. Khutoryanskiy, Macromolecular Bioscience 2003, 3, 283.
    [2] V. V. Khutoryanskiy, A. V. Dubolazov, Z. S. Nurkeeva, G. A. Mun, Langmuir 2004, 20, 3785.
    [3] Z. S. Nurkeeva, G. A. Mun, A. V. Dubolazov, V. V. Khutoryanskiy, Macromolecular bioscience 2005, 5, 424.
    [4] T. Ikawa, K. Abe, K. Honda, E. Tsuchida, Journal of Polymer Science: Polymer Chemistry Edition 1975, 13, 1505.
    [5] S. A. Sukhishvili, S. Granick, Macromolecules 2002, 35, 301.
    [6] C. Maltesh, P. Somasundaran, R. Kulkarni, S. Gundiah, Langmuir 1991, 7, 2108.
    [7] F. Bailey, R. Lundberg, R. Callard, Journal of Polymer Science Part A: General Papers 1964, 2, 845.
    [8] S. Yang, X. Yu, L. Wang, Y. Tu, J. X. Zheng, J. Xu, R. M. Van Horn, S. Z. Cheng, Macromolecules 2010, 43, 3018.
    [9] Y. Cohen, V. Prevysh, Acta polymerica 1998, 49, 539.
    [10] H. A. A. El-Rehim, E.-S. A. Hegazy, A. A. Hamed, A. E. Swilem, European Polymer Journal 2013, 49, 601.
    [11] T. Okubo, J. Okamoto, A. Tsuchida, Colloid and Polymer Science 2010, 288, 189.
    [12] V. V. Khutoryanskiy, Z. S. Nurkeeva, G. A. Mun, A. V. Dubolazov, Journal of applied polymer science 2004, 93, 1946.
    [13] D. E. Zhunuspayev, G. A. Mun, P. Hole, V. V. Khutoryanskiy, Langmuir 2008, 24, 13742.
    [14] Y. Chen, Y. Pang, J. Wu, Y. Su, J. Liu, R. Wang, B. Zhu, Y. Yao, D. Yan, X. Zhu, Langmuir 2010, 26, 9011.
    [15] C. Ding, S. Xu, J. Lin, X. Hu, W. Jian, J. Wang, J. Ma, S. Feng, Journal of Polymer Research 2012, 19, 1.
    [16] O. V. Khutoryanskaya, P. W. Morrison, S. K. Seilkhanov, M. N. Mussin, E. K. Ozhmukhametova, T. K. Rakhypbekov, V. V. Khutoryanskiy, Macromolecular bioscience 2014, 14, 225.
    [17] V. V. Khutoryanskiy, International journal of pharmaceutics 2007, 334, 15.
    [18] B.-S. Kim, S. W. Park, P. T. Hammond, Acs Nano 2008, 2, 386.
    [19] M. K. Chun, C. S. Cho, H. K. Choi, Journal of applied polymer science 2004, 94, 2390.
    [20] C. P. Sharma, Journal of applied polymer science 2006, 99, 506.
    [21] J. M. Oh, C. S. Cho, H. K. Choi, Journal of applied polymer science 2004, 94, 327.
    [22] Y. Tian, P. Ravi, L. Bromberg, T. A. Hatton, K. C. Tam, Langmuir 2007, 23, 2638.
    [23] X. Xiong, K. Tam, L. Gan, Macromolecules 2003, 36, 9979.
    [24] M. Paloma, S. Torrado, S. Torrado, Biomaterials 2003, 24, 1459.
    [25] B. Deutel, M. Greindl, M. Thaurer, A. Bernkop-Schnürch, Biomacromolecules 2007, 9, 278.
    [26] P. M. de la Torre, G. Torrado, S. Torrado, Journal of Biomedical Materials Research Part B: Applied Biomaterials 2005, 72, 191.
    [27] S. Saito, Colloid and Polymer Science 1982, 260, 613.
    [28] M. Bauer, C. Lautenschlaeger, K. Kempe, L. Tauhardt, U. S. Schubert, D. Fischer, Macromolecular bioscience 2012, 12, 986.
    [29] R. Hoogenboom, Angewandte Chemie International Edition 2009, 48, 7978.
    [30] C. Kim, S. C. Lee, J. H. Shin, J.-S. Yoon, I. C. Kwon, S. Y. Jeong, Macromolecules 2000, 33, 7448.
    [31] C. Kim, S. C. Lee, I. C. Kwon, H. Chung, S. Y. Jeong, Macromolecules 2002, 35, 193.
    [32] T. B. Bonné, K. Lüdtke, R. Jordan, C. M. Papadakis, Macromolecular Chemistry and Physics 2007, 208, 1402.
    [33] P. Persigehl, R. Jordan, O. Nuyken, Macromolecules 2000, 33, 6977.
    [34] S. C. Lee, Y. Chang, J.-S. Yoon, C. Kim, I. C. Kwon, Y.-H. Kim, S. Y. Jeong, Macromolecules 1999, 32, 1847.
    [35] G. Volet, V. Chanthavong, V. Wintgens, C. Amiel, Macromolecules 2005, 38, 5190.
    [36] R. Luxenhofer, R. Jordan, Macromolecules 2006, 39, 3509.
    [37] S. Zalipsky, C. B. Hansen, J. M. Oaks, T. M. Allen, Journal of pharmaceutical sciences 1996, 85, 133.
    [38] M. C. Woodle, C. M. Engbers, S. Zalipsky, Bioconjugate chemistry 1994, 5, 493.
    [39] O. Sedlacek, B. D. Monnery, S. K. Filippov, R. Hoogenboom, M. Hruby, Macromolecular rapid communications 2012, 33, 1648.
    [40] R. Luxenhofer, A. Schulz, C. Roques, S. Li, T. K. Bronich, E. V. Batrakova, R. Jordan, A. V. Kabanov, Biomaterials 2010, 31, 4972.
    [41] C.-H. Wang, C.-H. Wang, G.-H. Hsiue, Journal of controlled release 2005, 108, 140.
    [42] T. F. Tadros, "Applied surfactants: principles and applications", John Wiley & Sons, 2006.
    [43] D. Myers, "Surfaces, interfaces and colloids", Wiley-Vch New York etc., 1990.
    [44] M. Schick, The Journal of Physical Chemistry 1964, 68, 3585.
    [45] K. Holmberg, B. Jönsson, B. Kronberg, B. Lindman, Journal of Synthetic Lu-brication 2004, 20, 367.
    [46] M. N. Jones, Journal of colloid and interface science 1967, 23, 36.
    [47] M. Schwuger, Journal of colloid and interface science 1973, 43, 491.
    [48] N. J. Turro, B. H. Baretz, P. L. Kuo, Macromolecules 1984, 17, 1321.
    [49] P. Yan, J.-X. Xiao, Colloids and Surfaces A: Physicochemical and Engineering Aspects 2004, 244, 39.
    [50] E. D. Goddard, Colloids and Surfaces 1986, 19, 255.
    [51] S. Halacheva, J. Penfold, R. Thomas, Langmuir 2012, 28, 17331.
    [52] A. Bogomolova, M. Hruby, J. Panek, M. Rabyk, S. Turner, S. Bals, M. Steinhart, A. Zhigunov, O. Sedlacek, P. Stepanek, Journal of Applied Crystallography 2013, 46, 1690.
    [53] P. J. Kay, F. Treloar, Die Makromolekulare Chemie 1974, 175, 3207.
    [54] H. Okamoto, Y. Wada, Journal of Polymer Science: Polymer Physics Edition 1974, 12, 2413.
    [55] D. F. Anghel, J. L. Toca-Herrera, F. M. Winnik, W. Rettig, R. v. Klitzing, Langmuir 2002, 18, 5600.
    [56] C. Wang, K. Tam, The Journal of Physical Chemistry B 2005, 109, 5156.
    [57] I. Iliopoulos, J. Halary, R. Audebert, Journal of Polymer Science Part A: Polymer Chemistry 1988, 26, 275.
    [58] S. C. Lee, H. J. Lee, Langmuir 2007, 23, 488.
    [59] S. Das, M. T. Joseph, D. Sarkar, Langmuir 2013, 29, 1818.
    [60] Y. Matsumura, H. Maeda, Cancer research 1986, 46, 6387.
    [61] J.-Z. Du, X.-J. Du, C.-Q. Mao, J. Wang, Journal of the American Chemical Society 2011, 133, 17560.
    [62] C. Mora-Huertas, H. Fessi, A. Elaissari, International journal of pharmaceutics 2010, 385, 113.
    [63] H. Maeda, J. Wu, T. Sawa, Y. Matsumura, K. Hori, Journal of controlled release 2000, 65, 271.
    [64] D. Peer, J. M. Karp, S. Hong, O. C. Farokhzad, R. Margalit, R. Langer, Nature nanotechnology 2007, 2, 751.
    [65] W. Stockton, M. Rubner, Macromolecules 1997, 30, 2717.
    [66] S. A. Sukhishvili, S. Granick, Journal of the American Chemical Society 2000, 122, 9550.
    [67] N. A. Peppas, "Hydrogels in medicine and pharmacy", CRC press Boca Raton, FL, 1987.
    [68] N. A. Peppas, J. Klier, Journal of Controlled Release 1991, 16, 203.
    [69] T. Budtova, I. Suleimenov, Journal of Polymer Science Part A: Polymer Chemistry 1994, 32, 281.
    [70] Y. Tian, L. Bromberg, S. Lin, T. A. Hatton, K. C. Tam, Journal of Controlled Release 2007, 121, 137.
    [71] A. J. Bard, L. R. Faulkner, "Electrochemical methods: fundamentals and applications", Wiley New York, 1980.
    [72] J. Koetz, S. Kosmella, "Polyelectrolytes and nanoparticles", Springer Science & Business Media, 2007.
    [73] D. A. Skoog, F. J. Holler, S. R. Crouch, Cengage Learning, New Delhi 2007, 135.
    [74] F. M. Winnik, Chemical reviews 1993, 93, 587.
    [75] G. Bains, A. B. Patel, V. Narayanaswami, Molecules 2011, 16, 7909.
    [76] P.-G. De Gennes, "Scaling concepts in polymer physics", Cornell university press, 1979.
    [77] A. V. Dobrynin, R. H. Colby, M. Rubinstein, Macromolecules 1995, 28, 1859.
    [78] H. Sah, L. A. Thoma, H. R. Desu, E. Sah, G. C. Wood, International journal of nanomedicine 2013, 8, 747.
    [79] A. M. Bernard, "Molecular Modeling of Poly (2-ethyl-2-oxazoline)", ProQuest, 2008.
    [80] G. A. Mun, Z. S. Nurkeeva, V. V. Khutoryanskiy, G. S. Sarybayeva, A. V. Dubolazov, European polymer journal 2003, 39, 1687.
    [81] Z. S. Nurkeeva, G. A. Mun, V. V. Khutoryanskiy, A. D. Sergaziev, European polymer journal 2001, 37, 1233.
    [82] V. Prevysh, B.-C. Wang, R. Spontak, Colloid and Polymer Science 1996, 274, 532.

    下載圖示 校內：2025-08-26公開
    校外：2025-08-26公開
    QR CODE