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研究生:鄭經豪
論文名稱:類磷脂質高分子團聯共聚物之製備與其在癌症治療之應用
論文名稱(外文):Preparation of lipid-like block copolymer and its applications for cancer therapy
指導教授:莊祚敏薛敬和薛敬和引用關係
學位類別:碩士
校院名稱:國立交通大學
系所名稱:應用化學系所
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2005
畢業學年度:94
語文別:中文
論文頁數:50
中文關鍵詞:團聯高分子微胞藥物載體生物相容性
外文關鍵詞:Block copolymermicelledrug carrierbiocompatibility
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近幾年來類磷脂質高分子在生醫科技的應用上具有舉足輕重的地位,其優異的生物相容性以及類似於生物細胞膜的組成等特性都是備受矚目的。MPC高分子抗凝血的特性在各應用上都有不錯的研究成果,如生物晶片、人工血管、組織修復、藥物控制釋放等等。本論文主要是要研究以聚PLA-PMPC雙團聯共聚物,以作為治療癌症之奈米藥物載體。
在一系列的實驗中,聚乳酸(PLA)與MPC以原子轉移自由基聚合法合成PLA-PMPC。以透析法製備成高分子微胞,探討溶劑與粒徑的關係,改變溶劑組成比來獲得不同粒徑的微胞。利用1H-NMR、AFM、以及界面電位等測定出微胞的型態與結構。以HFW與Hela兩株細胞測試材料以及高分子微胞之細胞毒性,證實材料具有優異之生物相容性以及安全性。包覆疏水性抗癌藥物Doxorubicin,將其包覆情形、藥物釋放的行為、以及毒殺的效果等結果進行比較,探討此合成之高分子材料在治療癌症之藥物控制釋放系統上之應用價值。
中文摘要…………………………………………………………………i
英文摘要………………………………………………………………ii
誌謝…………………………………………………………………………iii
目錄……………………………………………………………………iv
圖索引…………………………………………………………………vi
表索引…………………………………………………………………viii
第一章 研究背景與動機………………………………………………1
第二章 相關理論與文獻………………………………………………4
2.1 含磷脂質材料簡介……………………………………………4
2.1.1 MPC單體……………………………………………4
2.1.2 含磷脂質單體—MPC之特性………………………4
2.2 含磷脂質高分子具有優異生物相容性之機制………………7
2.2.1 高分子含水之結構……………………………………7
2.2.2 磷脂質吸附於高分子表面……………………………7
2.2.3 蛋白質吸附於高分子表面…………………………7
2.2.4 蛋白質吸附數量……………………………………7
2.2.5 高分子自由水含量和蛋白質吸附的關係…………7
2.2.6 高分子表面吸附磷脂質和蛋白質之關係…………8
2.3 生物可降解性高分子………………………………………9
2.3.1 生物可降解定義……………………………………9
2.3.2 生物可降解機制……………………………………9
2.3.3 生物可降解性高分子簡介…………………………10
2.4 高分子微胞在藥物制放上的應用…………………………12
2.5 陰離子聚合反應原理………………………………………14
2.5.1 起始劑之種類………………………………………14
2.5.2 起始反應之方式……………………………………14
2.5.3 成長反應……………………………………………15
2.5.4 無終止反應與其特色………………………………15
2.6 原子轉移自由基聚合(ATRP) ………………………………16
2.6.1 起始反應機制………………………………………16
2.6.2 適用之單體…………………………………………16
2.6.3 觸媒與配位基………………………………………17
2.6.4 多元的聚合法與其特性……………………………18
第三章 實驗方法………………………………………………………21
3.1 實驗藥品……………………………………………………21
3.2 實驗儀器與裝置……………………………………………21
3.3 合成PLA-PMPC雙團聯共聚物……………………………22
3.4 鑑定與分析…………………………………………………23
3.5 臨界微胞濃度………………………………………………23
3.6 製備PLA-PMPC高分子微胞………………………………23
3.7 粒徑與介面電位分析………………………………………24
3.8 體外藥物釋放模擬…………………………………………24
3.9 細胞存活率與細胞毒殺實驗………………………………25
第四章 結果與討論……………………………………………………26
4.1 合成PLA-PMPC兩團聯共聚物……………………………26
4.2 臨界微胞濃度………………………………………………30
4.3 粒徑與介面電位分析………………………………………32
4.3.1 透析法製備高分子微胞……………………………32
4.3.2 表面電位分析………………………………………38
4.4 細胞存活率…………………………………………………39
4.5 體外藥物釋放模擬…………………………………………41
4.6 細胞毒殺實驗………………………………………………44
第五章 結論……………………………………………………………45
參考文獻………………………………………………………………46
1. P. Ehrlich, Collected study on immunology, John Wiley, New York, pp.441 (1906).
2. C. J. T. Hoes, J. Grootoonk, J. Feijen, P. J. Boon, and F. Kaspersen, Synthesis and biodistribution of immunoconjugates of a human lgM and polymeric drug carriers, J. Controlled Release, 1992; 19: 59
3. Y. Sadzuka, S. Nakai, A. Miyagishima, Y. Nozawa, and S. Hirota, Effects of administered route on tissue distribution and antitumor activity of polyethyleneglycol-coated liposomes containing adriamycin, Cancer Letters, 1997; 111: 77
4. J. C. Leroux, E. All�聱ann, F. De Jaeghere, E. Doelker, and R. Gurny, Biodegradable nanoparticles – From sustained release formulations to improved site specific drug delivery, J. Controlled Release, 1996; 39: 339
5. E. ALL, R. Emann, and E. D. Gurny, Drug loaded nanoparticles-Preparation method and drug targeting issues, Eur. J. Pharm. Biopharm., 1993; 39: 173
6. I. Brigger, C. Dubernet, and P. Couvreur, Nanoparticles in cancer therapy and diagnosis, Adv. Drug Deliv. Rev., 2002; 54: 631
7. M. C. Jones, J. C. Leroux, “Polymeric micelles – A new generation of colloidal drug carriers” Eur. J. Pharm. Biopharm., 1999, 48, 101
8. N. Oku, Y. Namba, S. Okada, “”Tumor accumulation of novel RES-avoiding liposomes Biochim. Biophys. Acta, 1992, 1126, 255
9. M Yokoyama, M Miyauchi, N Yamada, T Okano, Y Sakurai, K Kataoka, and S Inoue, “Characterization and anticancer activity of the micelle-forming polymeric anticancer drug adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer ” Cancer Res 1990 50: 1693-1700.
10. M Yokoyama, T Okano, Y Sakurai, H Ekimoto, C Shibazaki, and K Kataoka, “Toxicity and antitumor activity against solid tumors of micelle-forming polymeric anticancer drug and its extremely long circulation in blood.” Cancer Res 1991 51: 3229-3236.
11. K. Ishihara, T. Ueda, N. Nakabayashi, Preparation of phospholipids polymer as polymer hydrogel membrane, Polymer Journal, 1990; 22: 355
12. Ishihara K, Oshida H, Endo Y, Ueda T, Watanabe A, Nakabayashi N. Hemocompatibolity of human whole blood on polymers with a phosphorlipid polar group and its mechanism. J Biomed Mater Res 1992; 26: 1543-52
13. Ishihara K, Nomura H, Nhhara T, Kurita K, Iwasaki Y, Nakabayashi N. Why do phospholipid polymers reduce proteinadsorption? J Biomed Mater Res 1998; 39: 323-30
14. Kadoma Y, Nakabayashi N, Masuhara E, Yamauchi J. Synthesis and hemolysis of the polymer containing phosphorylcholine groups. Kobunshi Ronbushu 1978; 35: 423-7
15. Nakabayashi N, Williams D F. Preparation of non-thrombogenic materials using 2-methacryloyloxloxyethyl phosphorylcholine. Biomaterials 2003; 24: 2431-2435
16. Ishihara K, Ueda T, Nakabayashi N. preparation of phospholipids polymers and their properties as polymer hydrogel membrane. Polym. J. 1990; 22: 355-60
17. Sugiyama, K. and Aoki, H. “Surface modified polymer microspheres obtained by the emulsion copolymerization of 2-Methacryloyloxloxyethyl phosphorylcholine with various vinyl monomers” Polym. J. 1994, 26, 561
18. Ishihara K, Nomura H, Nhhara T, Kurita K, Iwasaki Y, Nakabayashi N. Why do phospholipid polymers reduce proteinadsorption? J Biomed Mater Res 1998; 39: 323-30
19. Ishihara K, Iwasaki Y, and Nakabayashi N,”Novel biomedical polymers for regulating serious biological reactions”(1998) Mater. Sci. Eng. C6,253.
20. Ishihara K, Oshida H, and Endo Y,”Henocompatibility of human whole blood on polymers with phospholipids polar group and its mechanism.”(1992) J. Biomed. Mater. Res. 26,1543.
21. Ishihara K, Oshida H, and Endo Y,”Effects of phospholipid adsorption on nonthrombogenicity of polymer with phospholipid polar group.”(1993) J. Biomed. Mater. Res. 27,1309.
22. Iwasaki Y, Tanaka S, and Hara M,”Stabilization of liposomes attached to polymer surfaces having phosphorycholine groups.”(1997) J. Colloid Interface Sci. 192,432.
23. Iwasaki Y, Ishihara K, and Nakabayashi N,”Newly designed polymers for artifical organs.”(1997) Recent Res. Devel. In polym. Sci. 1,37.
24. Rosen H, Kohn J, Leong K, Langer R, “Biodegradable polymers for controlled release system.” Controlled Released System(1998),83.
25. Li S, Cathy S M, “Further investigations on the hydrolytic degradation of poly(DL-lactide).”Biomaterials,(1999) 20:35-44.
26. Bader H, Ringsdorf H, Schmidt B, Angew. Chem.,123/124,457(1984)
27. Pratten M K, Lioyd J B, Horpel G, Ringsdorf H, “Micelle-forming block copolymers: Pinocytosis by macrophages and interaction with model membranes” Makromol. Chem. 186,725(1985)
28. Kwon G S, Natio M, Kataoka K, Yokoyama M, Sakurai Y, Okano T, “Block copolymer micelles as vehicles for hydrophobic drugs” Colloids and surfaces B:Biointerfaces, 2,429(1994).
29. Yokoyama M, Okano T, Sakurai Y, Ekimoto H, Shibazaki C, and Kataoka K, “Toxicity and antitumor activity against solid tumors of micelle-forming polymeric anticancer drug and its extremely long circulation in blood.” Cancer Research,51 3229-3236.
30. Granath K A, Kvist B E, “Molecular weight distribution analysis by gel chromatography on sephadex” Chromatogr J,28,69(1967).
31. Gregoriadis G, Ryman B E, “Fate of protein-containing liposomes injected into rats. An approach to the treatment of storage diseases” Eur. J. Biochem. ,24,485(1972).
32. Senior J H, “Fate and behaviour of liposomes in vivo: a review of controlling factors.” CRC Crit. Rev. Ther. Drug Carrier Syst. ,3:123(1987).
33. Lin D, Mori A, and Huang L, Biochemica et Biophysica Acta, 1104,95(1992).
34. Cao T, Munk P, Ramireddy C, Tuzar Z, Webber S E, ” Fluorescence studies of amphiphilic poly(methacrylic acid)-block-polystyrene-block-poly(methacrylic acid) micelles” Macromolecules, 24,6300(1991).
35. Duncan R, Kopekova-Rejmanova P, Strohalm J, Hume I, Cable H C, Pohl J, Lloyd B, Kopecek J, “Anticancer agents coupled to N-(2-hydroxypropyl)methacrylamide copolymers. I. Evaluation of daunomycin and puromycin conjugates in vitro.” Br. J. Cancer,55,165-174(1987).
36. Kataoka K, Kwon G, Yokoyama M, Okano T, Sakurai Y, “Block copolymer micelles as vehicles for drug delivery” J. Controlled Release,24,119-132(1993).
37. Kataoka K, ” Design of nanoscopic vehicles for drug targeting based on micellization of amphiphilic block copolymers” J.M.S.─ Pure Appl. Chem.,A31(11),1759(1994).
38. Dunn S E, Birndley A, Davis S S, Dacies M C, and Illum L, “Polystyrene-poly (ethylene glycol) (PS-PEG2000) particles as model systems for site specific drug delivery. 2. The effect of PEG surface density on the in vitro cell interaction and in vivo biodistribution.” Pharmacentical Research,11,1016 (1994).
39. D. Decker and P. Rempp, CR Hebd. Seances Acad. Sci., Ser. C 261 1977
40. Szwarc M. ” Living Polymers” Nature 1956,178,1168.
41. Szwarc M, Levy M, Milkovich R, ” Polymerization initiated by electron transfer to monomer: A new method of preparation of block polymers.” J. Am. Chem. Soc. 1956,78,2657.
42. Webster O W, ” Living polymerization methods.” Science 1991,251,887.
43. Matyjaszewski K, Gaynor S G, In Applied Polymer Science; Craver C D, Carracher C E, Jr. Eds. Pergamon Press:Oxford,Uk,2000;929.
44. Matyjaszewski K “Controlled Radical polymerization.” American Chemical Society: Washington, DC, 1998; Vol.685.
45. Matyjaszewski K, ”Controlled/Living Radical Polymerization: Progress in ATRP, NMP, and RAFT.” American Chemical Society: Washington, DC, 2000; Vol.768.
46. Wang J S, Matyjaszewski K , “Controlled/"living" radical polymerization. atom transfer radical polymerization in the presence of transition-metal complexes”J. Am. Chem. Soc. 1995,117,5614.
47. Kato M, Kamigaito M, Sawamoto M, Higashimura, T, “Polymerization of Methyl Methacrylate with the Carbon Tetrachloride/Dichlorotris- (triphenylphosphine)ruthenium(II)/Methylaluminum Bis(2,6-di-tert-butylphenoxide) Initiating System: Possibility of Living Radical Polymerization”Macromolecules 1995, 28, 1721.
48. Wang J S, Matyjaszewski K, “Controlled/"Living" Radical Polymerization. Halogen Atom Transfer Radical Polymerization Promoted by a Cu(I)/Cu(II) Redox Process” Macromolecules 1995,28,7901.
49. Percec V, Barboiu B, “ "Living" Radical Polymerization of Styrene Initiated by Arenesulfonyl Chlorides and CuI(bpy)nCl” Macromolecules 1995,28,7970.
50. Matyjaszewski K, Jo S M, Paik H J, Shipp D A, “An Investigation into the CuX/2,2'-Bipyridine (X = Br or Cl) Mediated Atom Transfer Radical Polymerization of Acrylonitrile” Macromolecules 1999,32,6431.
51. Davis K, Paik H J, Matyjaszewski K, “Kinetic Investigation of the Atom Transfer Radical Polymerization of Methyl Acrylate” Macromolecules 1999,32,1767.
52. Grimaud T, Matyjaszewski K, “Controlled/"Living" Radical Polymerization of Methyl Methacrylate by Atom Transfer Radical Polymerization” Macromolecules 1997,30,2216.
53. Kotani Y, Kato M, Kamigaito M, Sawamoto M, “Living Radical Polymerization of Alkyl Methacrylates with Ruthenium Complex and Synthesis of Their Block Copolymers” Macromolecules 1996,29,6979.
54. Granel C, Dubois P, J�臆�鏔e R, Teyssi�� P, “Controlled Radical Polymerization of Methacrylic Monomers in the Presence of a Bis(ortho-chelated) Arylnickel(II) Complex and Different Activated Alkyl Halides” Macromolecules 1996,29,8576.
55. Louie J, Grubbs R H, “Highly active iron imidazolylidene catalysts for atom transfer radical polymerization.”Chem. Commun. 2000,1479.
56. Pecec V, Barbois B, Neumann A, Ronda J C, Zhao M, “Metal-Catalyzed "Living" Radical Polymerization of Styrene Initiated with Arenesulfonyl Chlorides. From Heterogeneous to Homogeneous Catalysis” Macromolecules 1996,29,3665.
57. Patten T E, Matyjaszewski K, “Copper(I)-Catalyzed Atom Transfer Radical Polymerization” Acc. Chem. Res. 1999,32,895.
58. Cassebras M, Pascual S, Polton A, Tardi M, Vairon J P, “Synthesis of di- and triblock copolymers of styrene and butyl acrylate by controlled atom transfer radical polymerization” Macromol. Rapid Commun. 1999,20,261.
59. Miller P J, Matyjaszewski K, “Atom Transfer Radical Polymerization of (Meth)acrylates from Poly(dimethylsiloxane) Macroinitiators” Macromolecules 1999,32,8760.
60. Yinghua M, Yiqing T, Norman C B, and Steven P A, “Well-Defined Biocompatible Block Copolymers via Atom Transfer Radical Polymerization of 2-Methacryloyloxyethyl Phosphorylcholine in Protic Media” Macromolecules 2003,36,3475.
61. Kalyanasundaram K, Thomas J K, “Environmental effects on vibronic band intensities in pyrene monomer fluorescence and their application in studies of micellar systems” J. Am. Chem. Soc. 1977 99,2039.
62. Wihelm M, Zhao C L, Wang Y, Xu R, Winnik M A, Mura J L, Riess G, Croucher M D, “Poly(styrene-ethylene oxide) block copolymer micelle formation in water: a fluorescence probe study”Macromolecules 1991,24,1033.
63. Nagarajan R, Ganesh K, “Block copolymer self-assembly in selective solvents: Spherical micelles with segregated cores” J. Chem. Phys. 1989,90,5843
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