Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/3780
標題: 利用硬酯醇改質葡萄聚醣製備高分子液胞及其結構探討
Polymer Vesicles Self-Assembling from Octadecanol Modified Dextrans in Aqueous Solutions
作者: 黃筠喬
Huang, Yun-Chiao
關鍵字: dextran
高分子液胞
amphiphilic copolymers
polymeric vesicles
solvent replacement
double emulsion
multivesicle
溶劑置換法
葡萄聚醣
雙性高分子
二次乳化法
二階段二次乳化法
複合型高分子液胞
出版社: 化學工程學系所
引用: 參考文獻 1. Ringsdorf H. , B.S., J. Venzmer, , Angew. Chem. Int. Ed, 1998. 27(113). 2. Discher B. M., Y.Y.W., D.S. Ege, J. C.-H. Lee, F. S. Bates, D. E. Discher, D. A. Hammer, Science, 1999,284 .1143. 3. Discher D. E. ; Eisenberg A, Science 2002, (297): p. 967. 4. Bangham A. D., S.M.M., Watkins J. C., . J. Mol. Biol. , 1965. 13: p. 238-252. 5. New RRC, L.a.p.a., Oxford Univ. Press. 6. Discher B. M., W.Y.Y., Ege D. S., Lee J. C-M, Bates F. S., Discher D. E., Hammer D. A., Science, 1999. 284: p. 1143-1146. 7. Ahmed F., D.D.E., J. Controlled Release 2004, . 96: p. 37-53. 8. Zhang L., E.A., Science, 1995,. 268 p. 1728-1731. 9. Holder S. J., H.R.C., Sommerdijk N. A. J. M., Williams S. J., Jones R. G., Nolte R. , J. M., Chem. Commum. , 1998, : p. 1445-1446. 10. Battaglia G.;Ryan A. J., J. Phys. Chem. B. , 2006. 110: p. 10272-10279. 11. Stoenescu R.; Meier W., Chem. Commum. , 2002, : p. 3016-3017. 12. Uzun O., X.H., Jeoung E., Thibault R. J., Rotello V. M., , Chemi. Eur. J. , 2005. 11: p. 6916-6920. 13. Li Y.;Lokitz B. S.;McCormick C. L., Angew. Chem. Int. Ed., 2006. 45: p. 5792-5795. 14. Choi H. J., M.C.D., Nano Letters, 2005. 5: p. 2538-2542. 15. Dufes C.; Schätzlein A. G.; Tetley L; Gray A. I.;Watson D. G.; Oliver J. C;Couet W.;Uchegbu I. F., Pharmaceutical Research 2000. 17: p. 1250-1258. 16. Graff A., S.M., Gelder P. V., Meier W., Proc. Natl. Acad. , Science, 2002. 99: p. 5064-5068. 17. Ringsdorf H., S.B., Venzmer J., Angew. Chem. Int. Ed., 1988. 27: p. 113-158. 18. W., M., Chem. Soc. Rev, 2000. 29: p. 295-303. 19. Discher, B.M.W., Y. Y.; Ege, D. S.; Lee, J. C. M.; Bates, F. S.,; Discher, D. E.; Hammer, D. A. , Science 1999. 284(1143.). 20. Owen, R.L.S., J. K.; Breyer, E. D. , Electrophoresis, 2005. 26(735.). 21. Cruciani O.; Mannina, L.S., A. P.; Cametti, C.; Segre, A. , Molecules 2006. 11(334.). 22. Suhail Ahmad, N.A.G.a.P.D.B., J. Mol. Biol. , 1993. 234(1): p. 8-13. 23. Schmidt C.F.; Svoboda, K., Science 1993,(256): p. 952. 24. Photos, P.J.B., L.; Discher, B.; Bates, F. S.; Discher, D. E. . J. Control. Rel. , 2003,( 90): p. 323. 25. Najafi, F.S., M. N. , Biomaterials 2003,( 24): p., 1175. 88 26. Rijcken, C.J.F.S., O.; Hennink, W. E.; van Nostrum, C.F. , J. Control. Rel. , 2007, . 120(, 131.). 27. Rijcken, C.J.F.S., O.; Hennink, W. E.; van Nostrum, C.F. , J. Control. Rel. , 2007. 120(131.). 28. Jain S., B.F.S., Science, 2003. 300: p. 460-464.. 29. Discher D. E., E.A., Science, 2002. 297: p. 967-973. 30. Zhang L., E.A., Science, 1995. 268: p. 1728-1731. 31. Bellomo E. G.; Wyrsta M. D., P.L., Pochan D. J., Deming T. J., Nat. Mater., 2004. 3(244-248). 32. Bellomo E. G., W.M.D., Pakstis L., Pochan D. J., Deming T. J., , Nat. Mater., 2004. 3(244-248). 33. G., A.F.P.R.I.S., Molecular pharmaceutics 2006. 3(340-350). 34. Ahmed F., R.I.S.G., J. Control. Release 2006. 116(150-158.). 35. R.G.J.Willinghagen, A.E.F.M.a., Biochem,Pharmacol, 1963(12): p. 973-980. 36. 國立交通大學 應用化學系 聚葡萄聚醣標的型高分子抗癌前驅藥之製備及 其結構探討 2002. 37. R.G.J., M.A.E.F.a.W., Biochem,Pharmacol, 1963(12): p. 973-980. 38. Wolthuis V.D., J.J.K.-v.d.B., Macromolecules, 1997. 30: p. 3411-3412. 39. Hu Y, J.X., Ding Y, Ge H, Yuan Y, Yang C. , Biomaterials, 2003. 23: p. 3193-3201. 40. Rouzes, R.G., M. Leonard, A. De Sousa Delgado, E.Dellacherie, J. Biomed. Mater. Res. , 2000. 50: p. 557-565. 41. Coombes S. ;Tasker, M.L., Biomaterials, 1997. 18: p. 1153-1161. 42. Rouzes, A.D., M. ;Leonard, E.; Dellacherie,, J. Colloid Interface Sci, 2002. 253: p. 217-223. 43. Rouzes, M.L., A. ;Durand, E. Dellacherie, , Colloids Surfaces B: Biointerfaces, 2003. 32 p. 125-135. 44. Vansteenkiste, A.D.M.a.E.S., J.Bioact.Compat.Polym., 1992. 7: p. 4-14. 45. De J. S.J. ; S.C.De Smede, M.W.C.W., J.Demeester., Macromolecules, 2000. 200(33): p. 3680-3686. 46. Gref R., J.R., and Couvreur P. Macromolecules, 2002(35): p. 9861-9867. 47. Liebert T., S.H., Stephanie Hesse,and Thomas Heinze , J.AM.CHEM.SOC 2005(127): p. 10484-10485. 48. Gref J;Rodrigues, P.C., Macromolecules 2002(35): p. 9861. 49. Liebert T , H.S.H.S., and Heinze T,, J.AM.CHEM.SOC 2005(127): p. 10484-10485. 50. Deng Y; Li Y, Macromolecules 2006(39): p. 6590-6598. 51. Zhang Y., W.L., Rongkuan Jing, and Junlian Huang, J. Phys. Chem. B 2008. 112: 89 p. 16455–16460. 52. Zhang W;Shi L, Physical chemistry chemical physics 2004. 6(1): p. 109-115 53. Zhang W, L.S., * Kai Wu, and Yingli An, Macromolecules, 2005(38 (13)): p. 5743–5747. 54. Li X., K.Y.M., Xiping Ni, Chaobin He, Kam W. Leong, and Jun Li, J. Phys. Chem. B,2006. 110 (12): p. 5920–5926. 55. Zhang W .; Shi L. , W.K.a.A.Y., Macromolecules, 2005. 38(13): p. 5743–5747. 56. Wu P., M.S., Chen H., Di Q., and Wu C., Macromolecules, 1996(29 (1),): p. 277–281. 57. Deng Y., Y.L., and Wang X., Macromolecules 2006(, 39, ): p. 6590-6598. 58. Chen J.L , C.C., Yeh MK, J Microenca psule 2002. 19(3): p. 333~346. 59. Han K, L.K.D., Gao ZG,, J Cont rol Release 2001. 75(3): p. 259-270. 60. F, D.R.G.Q., J Pharm Sci ,, 2002. 91(3): p. 790-796. 61. Tirrell. H.G.S.a.D.A., Langmuir, 1991. 7(7). 62. Greenspan P, E.P.M., and Stanley D. Nile Red, Published March 1, 1985. 63. Yeo Y . , N.B., K. Park, , Biotechnol. Bioprocess. , 2001. 6: p. 213–230. 64. .A., J.R., Biomaterials 2000. 21: p. 2475–2490. 65. Ogawa Y . , M.Y., H. Okada, T. Yashiki, T.Shimamoto, Chem. Pharm. Bull. , 1988. 36 p. 1095–1103. 66. RRC, N., Liposomes. Oxford Univ. 67. K K.T., G.J., Haefele T., Meier W., Polymer 2005(46): p. 3540-3563. 68. Meng F., E.G.H.M., Feijen J., J. Control. Release, 2005. 101(187-198.). 69. G.H.;M.F.T.M., Journal of Controlled Release 2003. 91: p. 407–416. 70. Chu B., Laser Light Scattering, . 2nd Ed.Academic Press,New York, 1991. 71. W., B., In Light Scattering:Principles and Development;Brown,W.,Ed.;Clarendon Press:Oxford,. 1996. 13. 72. Wu, P.M., S.;Chen,H.;Qiang,D.;Wu,C, Marcromolecules, 1996(29): p. 277. 73. Palmer D.R.A.a.A.F., Biomacromolecules 2005(6): p. 2172-2181. 74. Meng F., H.C., Engbers G. H. M., Feijen J.,Macromolecules, 2003(36): p. 3004-3006. . 75. Ghoroghchian P. P., F.P.R., Susumu K., Blessington D., Macromolecules, 2005(102): p. 2922-2927. 76. Christian N. A., M.M.C., Ranka S. S., Li G., Frail P. R., Davis K. P., Bates F. S., Therien M. J., Ghoroghchian P. P., June C. H., Hammer D. A., Bioconjugate Chem, . 2007(18): p. 31-40. . 77. Ghoroghchian P. P., L.G., Levine D. H., Davis K. P., Macromolecules 2006( 39): p. 1673-1675. 78. Meng F.; Engbers G. H. M.;Feijen J., J. Control. Release 2005(101): p. 187-198. 90 79. Van D.W., S.K.Y.T., J. J. Bosch K.VD., Hennink W. E., Polymer 1997(38): p. 6235. 80. Li X., K.Y.M., Ni X., He C, Leong K.W.,and Li J, J.Phys.Chem.B. , 2006. 110((12),): p. 5920. 81. Tirrell. H.G.S., Langmuir, , 1991. 7(7). 82. Duhamel, H.S.a.J., Macromolecules, 2005 38(16). 83. Yildiz M. E., P.h.R.K., Robb I., Adamson D. H., , Polym. Adv. Technol, . 2007(18): p. 427-432. 84. Meng F., H.C., Engbers G. H. M., Feijen J., Macromolecules 2003(36): p. 3004-3006. 85. Liu K.H., S.-Y.C., Liu D.M,and Liu T.Y., Macromolecules 2008.41.: p. 6511-6516. 86. Goncalves C, J.A.M., and Francisco M.Gama,, Biomacromolecules 2007. 8: p. 392-398. 87. Chevance, C.G.D.L.M.S., Eur Biophys J, 2007. 36: p. 933-942. 88. Gao K.J., G.L., Xu B.Q, Journal of Polymer Science:Part A:Polymer Chemistry 2008. 46: p. 4889-4904. 89. I., L.R.G.G.D.A., J. Chem. Eng. Data,, 1962. 7(1): p. 100-101. 90. Soo P.L., A.E., J.Polym.SCI.Part B:POLYM.PHYS., 2004. 42. 91. Soo P.L., A.E., Journal of Polymer Science: Part B: Polymer Physics, 2004. 42: p. 923–938. 92. Shen H.; Eisenberg, A., Macromolecules, 2000. 33: p. 2561–2572. 93. Checot F. S.L., Gnanou Y,and Klok H., Angew. Chem. Int. Ed., 2002. 41(8). 94. Xu Y, L.S., Ma R, Zhang W, An Y,.Zhu X.X, polymer, 2007. 48: p. 1711. 95. Ma Y, T.C., and S. E. Webber, Macromolecules 1998. 31: p. 1773-1778. 96. Burchard, W., In Polysaccharides: Structural DiVersity and Functional Versatility. 2005: p. 189-236. 97. Kabanov A. V., T.K.B., V. A. Kabanov,K. Yu, and A. Eisenberg, J. Am. Chem. Soc. , 1998. 120: p. 9941-9942. 98. Akiyoshi K;Kobayashi S, S.S., Journal of controlled release, 1998. 54: p. 313-320. 99. S., S., Langmuir, 2007. 24(9): p. 4581–4588. 100. Keating, L.M.D.a.C.D., Langmuir, 2008. 24(23): p. 13565–13571. 101. Ghoroghchian P, G.L., Dalia H.Levine,Daniel A.Hammer, Macromolecules, 2006. 39: p. 1673-1675. 102. Li F, T.K., Antonius T. M. Marcelis, Frans A. M. Leermakers, Martien A. Cohen Stuart, and Ernst J. R. Sudhölter, Macromolecules, 2007. 40(2): p. 329–333. 103. Chiu H. C., Y.W.L., Y. F. Huang, C. K. Chuang, C. S. Chern, , Angew. Chem. Int. 91 Ed. , 2008, (47,): p. 1875. 104. 張海龍,林建強, 乳化溶劑揮發法在微球製備中的應用. China Academic Journal electronic publishing house, 1994. 105. Meng F, C.H., Gerard H. M. Engbers, and Jan Feijen, Macromolecules 2003. 36: p. 3004-3006. 106. S., C.H.C.L.Y.W.H.Y.F.C.C.K.C.C., Angew. Chem. Int. Ed., 2008. 47: p. 1875-1878. 107. Gao F, Z.-G.S., Wang P, Langmuir 2009. 25: p. 3832-3838. 108. Rosano, H.L.G., F. G.; Hidrot, J.-D. P., Colloids Surf. A, 1998. 138: p. 109-121. 109. D., C.P.C.B.W.M.F., BMC Biotechnol, 2002. 2: p. 9-17.
摘要: 在研究中,利用硬酯醇(Octadecanol)改質葡萄聚糖(dextran),並以二種製備方法製備高分子液胞。實驗中利用轉酯化反應將已活化的硬酯醇(18OH-CI) 成功改質葡萄聚醣鏈段得葡萄聚醣- 硬酯醇 dextran-g-octadecanol(DO)高分子,且利用核磁共振氫譜儀及紅外線光譜儀鑑定改質率。藉由調控硬酯醇的進料比,分別製備不同硬酯醇的碳鏈接枝比例(10、20、30 及40 mol %)之雙性高分子,其改質效率達九成。 利用溶劑置換法搭配不同初始水量的添加,可得不同尺寸大小之高分子液胞,以1H NMR、DLS 及TEM 分析於不同DMSO/H2O 比例下雙性高分子排列情形,當水加入高分子DMSO 溶液時,雙性高分子的烷鏈C18 鏈段因溶解度的降低進而因疏水作用趨使高分子以水為核心形成高分子液胞,且雙性高分子於臨界水含量(Critical water content,CWC)之後開始形成穩定高分子液胞結構,液胞粒徑大小不因進一步的溶劑置換而有所變化。由SLS 分析可知不同H2O 添加比例下,所形成的結構皆為高分子液胞,即Rg/Rh 比值趨近於1。此外,TEM 實驗中亦證實奈米高分子液胞內部可包覆水溶性螢光物calcein。 另一方面,採用二次乳化法製備微米高分子液胞(ca.1-27μm),結果指出,當DMSO 所佔比例上升會降低乳化液滴之界面張力而使液胞粒徑下降,而提高內部水相的W1 離子強度可穩定乳化液滴有助於液胞之形成,另外因滲透壓的提升而使液胞粒徑明顯增加。另於螢光物質包覆實驗中,可知小分子可穿透高分子液胞的胞膜,而較大分子量之物質則可包覆於液胞內部水相中。最後利用二階段二次乳化法,成功製備出複合型高分子液胞以非同心圓方式同時包覆數個尺寸較小高分子液胞於一較大尺寸液胞的內部水相中,藉提升高分子液胞於藥物釋放控制應用。
In this work, the biodegradable amphiphilic dextran-based copolymers comprising of different octadecanol contents are obtained by partial transesterification of activated octadecanol with dextran segments. The chemical compositions of copolymers are determined exactly by 1H-NMR and FT-IR measurements. A series of copolymers is utilized further to prepare polymeric vesicles by two approaches. These nano-scale polymeric assemblies are attained by self-assembly of amphiphilic copolymers in DMSO/H2O co-solvents and then dialysis against water. Combining the results of 1H-NMR and dynamic light scattering (DLS) measurements,the polymeric assemblies can be controlled well by adjusting the DMSO/H2O ratio used during self-assembly of copolymers. Importantly, the Rg/Rh ratios of the above polymeric assemblies examined by static light scattering (SLS) are approximately 1.0,confirming strongly that the structure of assemblies is presented in vesicle-like form.Moreover, the transmission electron microscopy (TEM) images show that thehydrophilic calcein molecules can be confined within the interior aqueous compartment of polymeric vesicles. On the other hand, the micro-scale polymeric vesicles with ca. 1~27μm in size can be obtained by double emulsion (W1/O/W2) process. Increasing the DMSO content of the DMSO/CHCl3 co-solvent reduces the vesicle size .Furthermore, elevating the ionic concentration in the W1 phase not only stabilizes efficiently the vesicle structure but also enlarges the vesicle size. From the data of fluorescence experiments, the small calcein probes can freely transport across the vesicular membrane, whereas the large FITC-dextran (Mw 4000 or 10000 g/mol) molecules within the aqueous compartment of vesicles are incapable of diffusing into outside aqueous phase. For expanding the applications of polymeric vesicles in drug delivery system, the multivesicle assemblies can be obtained further by suspending small vesicles (prepared in the first stage) in the W1 phase of the second-stage double emulsion process that was used to produce large vesicles.
URI: http://hdl.handle.net/11455/3780
其他識別: U0005-2707200918351500
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2707200918351500
Appears in Collections:化學工程學系所

文件中的檔案:

取得全文請前往華藝線上圖書館



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.