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研究生:蔡俊逸
研究生(外文):Chun-Yi Tsai
論文名稱:具有螢光探針親水性聚胜肽於疏水性藥物包覆之應用
論文名稱(外文):Hydrophilic polypeptide containing fluorescent probes for hydrophobic drugs encapsulation
指導教授:洪金龍
指導教授(外文):Jin-Long Hong
學位類別:碩士
校院名稱:國立中山大學
系所名稱:材料與光電科學學系研究所
學門:工程學門
學類:材料工程學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:英文
論文頁數:130
中文關鍵詞:β-環糊精藥物包埋高分子間氫鍵複合物二級結構聚胜肽
外文關鍵詞:secondary structurepolypeptideβ-cyclodextrindrug loadingpyrenehydrogen-bonded interpolymer complexes
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水溶性高分子間氫鍵複合物(hydrogen-bonded intepolymer complex,H-IPC)是由極性很大的水溶性高分子所組成,但複合物內部卻具有極高的疏水性質,本研究利用水溶性聚胜肽PPM作為質子的接受者,與質子的供應者聚丙烯酸PAA來形成H-IPC複合物,並使用此H-IPC複合物作為藥物包埋之用。水溶性聚胜肽PPM具有谷胺酸主鏈、親水醚(ether)基側鏈及尾端芘(pyrene)螢光感應基,而pyrene尾端基在疏水及親水性環境中,其於373 nm與383 nm處之螢光放射峰強度比(I1/I3)有極敏銳之變化,本實驗使用I1/I3值來探測形成H-IPC時及進一步藥物包埋時之親疏水性之變化。 在第二章中,將合成新的水溶性聚胜肽PPC具有谷胺酸主鏈、β-環糊精(β-Cyclodextrins)基側鏈及尾端芘(pyrene)螢光感應基,β-環糊精具有親水性的外環而分子內部為疏水性質,常應用於包覆疏水性藥物,本研究利用水溶性聚胜肽PPC乘載疏水性藥物,以及利用螢光放射峰強度比(I1/I3) 進一步藥物包埋時之親疏水性之變化。
Water soluble hydrogen-bonded interpolymer complexes (H-IPC) are composed of two highly polar polymers, of which one is a proton donor and the other is a proton acceptor. In this study, water-soluble polypeptide PPM was used as the proton acceptor to bind with proton-donating polyacrylic acid (PAA), rendering H-IPC for drug loading. The target polypeptide PPM consists of glutamate main chain, hydrophilic etheric side chain and a terminal pyrene as fluorescent sensing groups. Emission intensity ratio (I1/I3) of pyrene at 373 nm and 383 nm was used as fluorescence probe to sensing the environmental change around the pyrene terminal of PPM. Therefore, variation of I1/I3 can be used to correlate the morphological change of PPM upon forming H-IPC with PAA and upon further drug loading. In the second chapter, the target water-soluble polypeptide PPC consists of glutamate main chain, β-cyclodextrin side chain and a terminal pyrene as fluorescent sensing groups. β-cyclodextrin has a hydrophilic outer ring and hydrophobic cavity. It is often used to hydrophobic drugs loading. In this study, water-soluble polypeptide PPC was used to hydrophobic drugs loading, variation of I1/I3 can be used to correlate the morphological change of PPC and upon further drug loading.
Chinese Abstract.............................................………………………………….......…..i
English Abstract....................................................…………………………………….ii
Outline of Contents...…………………….....………....………....…………........…....iii
List of Figure……………………………………………………………..…....….......vi
List of Scheme............................................................................................….............xiv
List of Table..................................................................................................................xv
Chapter 1.
Hydrogen-bonded interpolymer complex between hydrophilic polypeptide and poly(acrylic acid)
1-1. Introduction...........................................................................................................1
1-2. Experimental…......................................................................................................4
1-2-1. Materials..............................................................................................................4
1-3. Characterization..................................................................................................11
1-4. Results and discussion.........................................................................................12
1-4-1. Synthesis of Py-NH2 from Py-OH…………………………………………….12
1-4-2. Synthesis and characterization of PPM...............................................................14
1-4-3. Secondary structure of Py-PPLG and PPM……................................................19
1-4-4. ACQ character of PPM……………………………………...…........................22
1-4-5. CMC of the aqueous PPM and PPM/PAA………………………………….…24
1-4-6. DLS and transmittance of PPM/DOX and PPM/PAA/DOX………………..….31
1-4-7. In vitro doxorubicin (Dox) release…………………………….….……………33
1-5. Conclution………................................................................................................50
1-6. References ….......................................................................................................51
Chapter 2.
Hydrophilic polypeptide containing cyclodextrin graft and its complex with hydrophobic drug
2-1. Introduction.........................................................................................................58
2-2. Experimental…....................................................................................................60
2-2-1. Materials............................................................................................................60
2-3. Characterization..................................................................................................66
2-4. Results and discussion.........................................................................................67
2-4-1. Syntheses of β-CD-N3 and PPC…………………………………………….….67
2-4-2. Secondary structure of Py-PPLG and PPC……................................................74
2-4-3. ACQ character of PPC……………………………………...…........................78
2-4-4. CMC of the aqueous PPM and PPC……………………….……………….….80
2-4-5. DLS and transmittance of PPM/DEX and PPC/DEX………………………….86
2-4-6. In vitro release of DEX…………………………………….….….……………88
2-5. Conclution………..............................................................................................101
2-6. References …......................................................................................................102
Supporting information...........................................................................................106
1.Ikawa, T.; Abe, K.; Honda, K.; Tsuchida, E. Interpolymer complex between poly(ethylene oxide) and poly(carboxylic acid). J. Polym. Sci., Polym. Chem. Ed. 1975, 13, 1505−1514.
2.Ohno, H.; Matsuda, H.; Tsuchida, E. Aggregation of poly(methacrylic acid)-poly(ethylene oxide) complex in aqueous medium. Makromol. Chem. 1981, 182, 2267−2275.
3.Iliopoulos, I.; Audebert, R. Influence of concentration, molecular weight and degree of neutralization of polyacrylic acid on interpolymer complexes with polyoxyethylene. Polym. Bull., 1985, 13, 171−178.
4.Hemker, D. J.; Garza, V.; Frank, C. W. Complexation of poly(acrylic acid) and poly(methacrylic acid) with pyrene-end-labeled poly(ethylene glycol): pH and fluorescence measurements. Macromolecules, 1990, 23, 4411−4418.
5.Khutoryanskiy, V. V.; Dubolazov, A. V.; Nurkeeva, Z. S.; Mun, G. A. pH effects in the complex formation and blending of poly(acrylic acid) with poly(ethylene oxide). Langmuir, 2004, 20, 3785−3790.
6.Klenina, O. V.; Fain, E. G. Phase separation in the system polyacrylic acid-polyacrylamide-water. Polym. Sci., 1981, 23, 1439−1446.
7.Eustace, D. J.; Siano, D. B.; Drake, E. N. Polymer compatibility and interpolymer association in the poly(acrylic acid)−polyacrylamide−water ternary system. J. Appl. Polym. Sci., 1988, 35, 707−716.
8.Staikos, G.; Karayanni, K.; Mylonas, Y. Complexation of polyacrylamide and poly(N-isopropylacrylamide) with poly(acrylic acid). The temperature effect. Macromol. Chem. Phys., 1997, 198, 2905−2915.
9.Aoki, T.; Kawashima, M.; Katono, H.; Sanui, K.; Ogata, N.; Okano, T.; Sakurai, Y. Temperature-responsive interpenetrating polymer networks constructed with poly(acrylic acid) and poly(N,Ndimethylacrylamide). Macromolecules, 1994, 27, 947−952.
10.Khutoryanskiy, V. V; Staikos, G. Hydrogen-Bonded Interpolymer Complexes: Formation, Structure and Applications, World Scientific: Singapore, 2009.
11.Tsuchida, E.; Abe, K. Interactions between macromolecules in olution and intermacromolecular complexes. Adv. Polym. Sci., 1982,45, 1−119.
12.Ozeki, T.; Yuasa, H.; Kanaya, Y. Controlled release from solid dispersion composed of poly(ethylene oxide)−Carbopol interpolymer complex with various cross-linking degrees of Carbopol. J. Controlled Release, 2000, 63, 287−295.
13.Lele, B. S.; Hoffman, A. S. Mucoadhesive drug carriers based on complexes of poly(acrylic acid) and PEGylated drugs having hydrolysable PEG−anhydride−drug linkages. J. Controlled Release, 2000, 69, 237−248.
14.Chun, M.-K.; Cho, C.-S.; Choi, H.-K. Mucoadhesive drug carrier based on interpolymer complex of poly(vinyl pyrrolidone) and poly(acrylic acid) prepared by template polymerization. J. Controlled Release, 2002, 81, 327−334.
15.Umana, E.; Ougizawa, T.; Inoue, T. Preparation of new membranes by complex formation of itaconic acid−acrylamide copolymer with polyvinylpyrrolidone: studies on gelation mechanism by light scattering. J. Membr. Sci., 1999, 157, 85−96.
16.Yilong Cheng, Chaoliang He, Chunsheng Xiao, Jianxun Ding, Xiuli Zhuang and Xuesi Chen, Polym. Chem., 2011, 2, 2627–2634
17.Yung-Chih Lin, Po-I Wang and Shiao-Wei Kuo, Soft Matter, 2012, 8, 9676–9684
18.Li-Yang Lin, Po-Chiao Huang, Deng-Jie Yang, Jhen-Yan Gao and Jin-Long Hong, Polym. Chem., 2016, 7, 153–163.
19.Yung-Chih Lin and Shiao-Wei Kuo, Polym. Chem., 2012, 3, 162–171.
20.Th. förster and K. Kasper, Z. Phys. Chem., 1954, 1, 275
21.J. Malkin, Photophysical and Photochemical Properties of Aromatic Compounds, CRC Press, Boca Raton, 1992.
22.Uchegbu IF, Sadiq L, Arastoo M, Gray AI, Wang W, Waigh RD et al, Int J Pharm, 2001, 224, 185–199.
23.Winnik FM, Chem Rev, 1993, 93, 587–614.
24.Lin Y and Alexandridis P, Langmuir, 2002, 18, 4220–4231.
25.Bokias G, Mylonas Y, StaikosG,BumbuGGandVasile C, Macromolecules, 2001, 34, 4958–4964.
26.Fischer A, Houzelle MC, Hubert P, Axelos AV, Geoffroy-Chapotot C, Carre MC et al, Langmuir, 1998, 14, 4482–4488
27.Philippova OE, Volkov EV, Sitnikova NL and Khokhlov AR, Biomacromolecules, 2001, 2, 483–490.
28.Kalyanasundaram K and Thomas JK, J Am Chem Soc, 1997, 99, 2039–2044.
29.Noda T and Morishima Y, Macromolecules, 1999, 32, 4631–4640.
30.D.C. Dong, M.A. Winnik, Photochem. Photobiol., 1982, 35, 17.
31.Yung-Chih Lin, Shiao-Wei Kuo, J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 321–329
32.Gabriel, S. Ber. Dtsch. Chem. Ges. 1887, 20, 2224–2236.
33.Zhe Yang, Xiaofang Zhang, Xingen Luo, Qing Jiang, Jie Liu, and Zhaozhong Jiang, Macromolecules, 2013, 46, 1743−1753
34.Jinjian Liu, Hongzhang Deng, Qiang Liu,a Liping Chu, Yumin Zhang, Cuihong Yang, Xuefei Zhao, Pingsheng Huang, Liandong Deng, Anjie Dong and Jianfeng Liu, Nanoscale, 2015, 7, 4451–4460.
35.C. S. Xiao, C. W. Zhao, P. He, Z. H. Tang, X. S. Chen and X. B. Jing, Macromol. Rapid Commun., 2010, 31, 991–997.
36.A. C. Engler, H. I. Lee and P. T. Hammond, Angew. Chem., Int. Ed., 2009, 48, 9334–9338.
37.A. C. Engler, A. Shukla, S. Puranam, H. G. Buss, N. Jreige andP. T. Hammond, Biomacromolecules, 2011, 12, 1666–1674.
38.Zhang, Y.; Lu, H.; Lin, Y.; Cheng, J, Water-Soluble Polypeptides with Elongated, Charged Side Chains Adopt Ultrastable Helical Conformations; Macromolecules, 2011, 44, 6641 − 6644.
39.Aichun Dong, Ping Huang, and Winslow S . Caughey, Biochemistry, 1990, 29, 3303-3308.
40.H. B. Du, R. N. Wickramasinghe, and X. H. Qian, J. Phys. Chem. B., 2010, 114, 16594–16604.
41.Rangarajan B, Coons LS and Scranton AB, Biomaterials, 1996, 17,649–661.
42.Chen H-L and Morawetz H, Eur Polym J, 1983, 19, 923–928.
43.Bednar B, Li Z, Huang Y, Chang L-CP and Morawetz H, Macromolecules, 1985, 18, 1829–1833.
44.Hemker DJ, Garza V and Frank CW, Macromolecules, 1990, 23, 4411–4418.
45.Wang Y and Morawetz H, Macromolecules, 1989, 22, 164–167.
46.Turro NJ, Caminati G and Kim J, Macromolecules, 1991, 24, 4054–4060.
47.Sivadasan K, Somasundaran P and Turro NJ, Colloid Polym Sci, 1991, 269, 131–137.
48.Soutar I,SwansonL, Thorpe FGandZhuC, Macromolecules, 1996, 29,918–924.
49.Nurkeeva ZS, Mun GA and Khutoryanskiy VV, Polym Sci, 2001, B43, 148–157.
50.H. Yin and Y. H. Bae, Eur. J. Pharm. Biopharm., 2009, 71, 223.
51.A. Di Crescenzo, D. Velluto, J. A. Hubbell and A. Fontana, Nanoscale, 2011, 3, 925.
52.Anand, R., Ottani, S., Manoli, F., Manet, I., Monti, S., RSC Adv., 2012 2, 2346–2357.
53.Hayakawa, E., Furuya, K., Kuroda, T., Moriyama, M., Kondo, A., Chem. Pharm. Bull., 1991, 39, 1282–1286.
54.M.J. Fonseca, E.C.A. van Winden, D.J.A. Crommelin, European Journal of Pharmaceutics and Biopharmaceutics, 1997, 43, 9- 17.
55.Zoltán Fülöp, Ruxandra Gref , Thorsteinn Loftsson, International Journal of Pharmaceutics, 2013, 454, 559–561.
1.H. A. Klok and S. Lecommandoux, Adv. Mater., 2001, 13, 1217–1229.
2.M. Sela and E. Katchalski, Adv. Protein Chem., 1959, 14, 391–477.
3.J. Kopacek, J. Controlled Release, 1990, 11, 279–290.
4.J. X. Ding, C. S. Xiao, L. Zhao, Y. L. Cheng, L. L. Ma, Z. H. Tang, X. L. Zhuang and X. S. Chen, J. Polym. Sci., Part A:Polym. Chem., 2011, 49, 2665–2676.
5.J. Y. Su, R. S. Hodges and C. M. Kay, Biochemistry, 1994, 33, 15501–15510.
6.C. L. He, C. W. Zhao, X. H. Guo, Z. J. Guo, X. S. Chen, X. L. Zhuang, S. Y. Liu and X. B. Jing, J. Polym. Sci., Part A: Polym. Chem., 2008, 46, 4140–4150.
7.G. Wenz, Angew. Chem., Int. Ed. Engl., 1994, 33, 803–822.
8.Saenger, W., Angew. Chem., Int. Ed. Engl., 1980, 19, 344.
9.Uekama, K., Yakugaku Zasshi, 1981, 101, 857.
10.Szejtli, J., J. Inclusion Phenom., 1983, 1, 135.
11.C. C. Rusa, T. A. Bullions, J. Fox, F. E. Porbeni, X. Wang and A. E. Tonelli, Langmuir, 2002, 18, 10016–10023.
12.D. R. Yei, S. W. Kuo, H. K. Fu and F. C. Chang, Polymer, 2005, 46, 741–750.
13.F.J. Otero-Espinar, J.J. Torres-Labandeira, C. Alvarez-Lorenzo, J. Blanco-Méndez, J. DRUG DEL. SCI. TECH., 2010, 20, 289-301.
14.Kaneto Uekama, Fumitoshi Hirayama, and Tetsumi Irie, Chem. Rev., 1998, 98, 2045-2076.
15.A. Harada, J. Li and M. Kamachi, Nature, 1994, 370, 126–128.
16.S. C. Chan, S. W. Kuo and F. C. Chang, Macromolecules, 2005, 38, 3099–3107.
17.C. W. Tu, S. W. Kuo and F. C. Chang, Polymer, 2009, 50, 2958–2966.
18.K. L. Liu, Z. Zhang and J. Li, Soft Matter, 2011, 7, 11290–11297.
19.Th. förster and K. Kasper, Z. Phys. Chem., 1954, 1, 275.
20.Uchegbu IF, Sadiq L, Arastoo M, Gray AI, Wang W, Waigh RD et al, Int J Pharm, 2001, 224, 185–199.
21.Winnik FM, Chem Rev, 1993, 93, 587–614.
22.Lin Y and Alexandridis P, Langmuir, 2002, 18, 4220–4231.
23.Bokias G, Mylonas Y, StaikosG,BumbuGGandVasile C, Macromolecules, 2001, 34, 4958–4964.
24.Fischer A, Houzelle MC, Hubert P, Axelos AV, Geoffroy-Chapotot C, Carre MC et al, Langmuir, 1998, 14, 4482–4488
25.Philippova OE, Volkov EV, Sitnikova NL and Khokhlov AR, Biomacromolecules, 2001, 2, 483–490.
26.Kalyanasundaram K and Thomas JK, J Am Chem Soc, 1997, 99, 2039–2044.
27.Noda T and Morishima Y, Macromolecules, 1999, 32, 4631–4640.
28.Yilong Cheng, Chaoliang He, Chunsheng Xiao, Jianxun Ding, Xiuli Zhuang and Xuesi Chen, Polym. Chem., 2011, 2, 2627–2634
29.Yung-Chih Lin and Shiao-Wei Kuo, Polym. Chem., 2012, 3, 162–171.
30.Yung-Chih Lin, Po-I Wang and Shiao-Wei Kuo, Soft Matter, 2012, 8, 9676–9684.
31.C. S. Xiao, C. W. Zhao, P. He, Z. H. Tang, X. S. Chen and X. B. Jing, Macromol. Rapid Commun., 2010, 31, 991–997.
32.A. C. Engler, H. I. Lee and P. T. Hammond, Angew. Chem., Int. Ed., 2009, 48, 9334–9338.
33.A. C. Engler, A. Shukla, S. Puranam, H. G. Buss, N. Jreige andP. T. Hammond, Biomacromolecules, 2011, 12, 1666–1674.
34.Zhang, Y.; Lu, H.; Lin, Y.; Cheng, J, Water-Soluble Polypeptides with Elongated, Charged Side Chains Adopt Ultrastable Helical Conformations; Macromolecules, 2011, 44, 6641 − 6644.
35.Matsui, Y.; Yokoi, T.; Mochida, K. Chem. Lett., 1976, 5, 1037.
36.Aichun Dong, Ping Huang, and Winslow S . Caughey, Biochemistry, 1990, 29, 3303-3308.
37.Jeon, S. Choo, J., Sohn D., Lee, S. N. Polymer, 2001, 42, 9915.
38.H. B. Du, R. N. Wickramasinghe, and X. H. Qian, J. Phys. Chem. B., 2010, 114, 16594–16604.
39.Ho Sang Jung, Taekyung Lee, Keun Kwon, Hyoung Seop Kim, Sei Kwang Hahn, and Chong Soo Lee, ACS Appl. Mater. Interfaces, 2015, 7, 9598−9607.
40.Rabia Mateen, Todd Hoare, International Journal of Pharmaceutics, 2014, 472, 315-326.
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