PPEGMEA-g-PBLG两亲性接枝共聚物的合成及其作为阿霉素输送载体的研究

doi:10.6023/cjoc201310043

有机化学 ›› 2013, Vol. 33 ›› Issue (12): 2520-2527.DOI: 10.6023/cjoc201310043 上一篇下一篇

研究论文

PPEGMEA-g-PBLG两亲性接枝共聚物的合成及其作为阿霉素输送载体的研究

蔡晓冰^a, 胡薇^b, 陆国林^c, 黄晓宇^c

a 同济大学附属上海第十人民医院骨科上海 200072;
b 第二军医大学附属长海医院普四科上海 200433;
c 中国科学院上海有机化学研究所上海 200032

收稿日期:2013-10-26 修回日期:2013-11-11 发布日期:2013-11-14
通讯作者: 胡薇，黄晓宇 E-mail:huweicj@163.com；xyhuang@mail.sioc.ac.cn
基金资助:
国家自然科学基金(Nos. 81171737，21174158)资助项目.

Synthesis of PPEGMEA-g-PBLG Amphiphilic Graft Copolymer and Its Research as Doxorubicin Delivery Vectors

Cai Xiaobing^a, Hu Wei^b, Lu Guolin^c, Huang Xiaoyu^c

a Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072;
b Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433;
c Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032

Received:2013-10-26 Revised:2013-11-11 Published:2013-11-14
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 81171737, 21174158).

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摘要/Abstract

首先利用单电子转移活性自由基聚合(SET-LRP)制备了聚甲基醚聚乙二醇丙烯酸酯(PPEGMEA)主链，再通过二异丙基氨基锂(LDA)攫取羰基α-位活泼氢合成了含溴的PPEGMEA-Br，通过亲核取代反应和还原反应两步制备得到了大分子开环聚合引发剂PPEGMEA-NH₂. 然后采用grafting-from策略，PPEGMEA-NH₂引发γ-苄基-L-谷氨酸酯五元环酸酐(BLG-NCA)的开环聚合，合成了结构规整的两亲性接枝共聚物PPEGMEA-g-PBLG. 接着，以PPEGMEA-g-PBLG为药物载体，负载了阿霉素(DOX). 利用紫外吸收光谱法测定了载药胶束的载药量，载药胶束的载药量最高可达到32.3%，载药胶束的体外药物释放具有很好的药物缓释特性.

关键词: 两亲性接枝共聚物, 单电子转移活性自由基聚合, 阿霉素：药物载体

The poly[poly(ethylene glycol) methyl ether acrylate] (PPEGMEA) backbone was first prepared by single electron transfer-living radical polymerization (SET-LRP). The backbone was treated with lithium diisopropylamide (LDA) and 2-bromoisobutyryl bromide at －78 ℃ to give Br-containing PPEGMEA-Br. PPEGMEA-NH₂ macroinitiator was then prepared by successive substitution and reduction reactions. A series of well-defined PPEGMEA-g-PBLG graft copolymers were synthesized by ring-opening graft polymerization of γ-benzyl-L-glutamate-N-carboxyanhydride (BLG-NCA) via grafting-from technique. A series of doxorubicin (DOX)-loaded polymeric micelles based on PPEGMEA-g-PBLG amphiphilic graft copolymers were prepared. The drug loading content (DLC) was measured by UV and the DLC of polymeric micelles was found to be as high as 32.3%. The drug release in vitro showed good delayed drug release feature.

Key words: amphiphilic graft copolymer, single electron transfer-living radical polymerization, doxorubicin, drug carrier

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蔡晓冰, 胡薇, 陆国林, 黄晓宇. PPEGMEA-g-PBLG两亲性接枝共聚物的合成及其作为阿霉素输送载体的研究[J]. 有机化学, 2013, 33(12): 2520-2527.

Cai Xiaobing, Hu Wei, Lu Guolin, Huang Xiaoyu. Synthesis of PPEGMEA-g-PBLG Amphiphilic Graft Copolymer and Its Research as Doxorubicin Delivery Vectors[J]. Chin. J. Org. Chem., 2013, 33(12): 2520-2527.

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参考文献

[1] Ryu, S. W.; Asada, H.; Hirao, A. Macromolecules 2002, 35, 7191.

[2] Li, A.; Lu, Z.; Zhou, Q.; Qiu, F.; Yang Y. J. Polym. Sci. Polym. Chem. 2006, 44, 3942.

[3] Segalman, R. A. Science 2008, 321, 919.

[4] Tang, C. B.; Lennon, E. M.; Fredrickson, G. H.; Kramer, E. J.; Hawker, C. J. Science 2008, 322, 429.

[5] Xi, C. B.; Yang, D.; Li, J.; Yan, J. J.; Hu, J. H. Chin. J. Org. Chem. 2012, 32, 2166 (in Chinese). (席陈彬, 杨东, 李静, 晏建军, 胡建华, 有机化学, 2012, 32, 2166.)

[6] Taton, K. S.; Guire, P. E. Biointerfaces 2002, 24, 123.

[7] Liu, T.; Zhang, Y. F.; Liu, S. Y. Chin. J. Polym. Sci. 2013, 31, 924.

[8] Kataoka, K.; Harada, A.; Nagasaki, Y. Drug Delivery Rev. 2001, 47, 113.

[9] Moeser, G. D.; Green, W. H.; Laibinis, P. E.; Linse, P.; Hatton, T. A. Langmuir 2004, 20, 5223.

[10] Zhang, M. F.; Estourne, C.; Bietsch, W.; Muller, A. H. E. Adv. Funct. Mater. 2004, 14, 871.

[11] Lutz, J. F.; Stiller, S.; Hoth, A.; Kaufner, L.; Pison, U.; Cartier, R. Biomacromolecules 2006, 7, 3132.

[12] Gu, L. N.; Shen, Z.; Feng, C.; Li, Y. G.; Lu, G. L.; Huang, X. Y.; Wang, G. W.; Huang, J. L. J. Mater. Chem. 2008, 18, 4332.

[13] Zheng, X. L.; Gao, H. S.; Ding, A. S.; Li, Y. J. Chin. J. Org. Chem. 2013, 33, 1509 (in Chinese). (郑兴良, 高鸿盛, 丁爱顺, 李永军, 有机化学, 2013, 33, 1509.)

[14] Kwon, G.. S.; Kataoka, K. Adv. Drug Delivery Rev. 1995, 16, 295.

[15] Kwon, G. S. Crit. Rev. Ther. Drug Carr. Syst. 1998, 15, 481.

[16] Lee, E. S.; Na, K.; Bae, Y. H. J. Controlled Release 2003, 91, 103.

[17] Lee, E. S.; Shin, H. J.; Na, K.; Bae, Y. H. J. Controlled Release 2003, 90, 363.

[18] Lee, E. S.; Oh, K. T.; Kim, T.; Youn, Y. S.; Bae, Y. H. J. Controlled Release 2007, 123, 19.

[19] Wang, C. H.; Wang, C. H.; Hsiue, G. H. J. Controlled Release 2005, 108, 140.

[20] Lo, C. L.; Huang, C. K.; Lin, K. M.; Hsiue, G. H. Biomaterials 2007, 28, 1225.

[21] Allen, T. M.; Cullis, P. R. Science 2004, 303, 1818.

[22] Oh, I.; Lee, K.; Kowon, H. Y.; Lee, Y. B.; Shin, S. C.; Cho, C. S.; Kim, C. K. Int. J. Pharm. 1999, 181, 107.

[23] Kataoka, K.; Harada, A.; Nagasaki, Y. Drug Delivery Rev. 2001, 47, 113.

[24] Torchil, IN. V. P. Adv. Drug Delivery Rev. 2002, 54, 235.

[25] Hu, Y.; Jiang, X.; Ding, Y. Biomaterials 2003, 24, 2395.

[26] Yokoyama, M.; Kataoka, K.; Inoue, S. J. Controlled Release l990, 11, 269.

[27] Hayashi, T.; Iizuka, Y.; Oya, M.; Iwatsuki, M. Polym. J. 1993, 25, 481.

[28] Genove, E.; Shen, C.; Zhang, S. Biomaterials 2005, 26, 3341.

[29] Wang, H. Y.; Xu, K. J.; Liu, L. H. Biomaterials 2010, 31, 2874.

[30] Lesley, W. C.; Wang, L. J.; Dixon, B. K. Biomaterials 2010, 31, 6154.

[31] He, P.; Zhao, C. W.; Xiao, C. S.; Tang, Z. H.; Chen, X. S. Chin. J. Polym. Sci. 2013, 31, 318.

[32] Pan, S. R.; Shi, F.; Huang, N. F. Chin. J. Biomed. Eng. 1993, 12, 161 (in Chinese). (潘仕荣, 施锋, 黄宁芳, 中国生物医学工程学学报, 1993, 12, 161.)

[33] Mori, H.; Müller, A. H. E. Prog. Polym. Sci. 2003, 28, 1403.

[34] Guyot, A.; Tauer, K. Adv. Polym. Sci. 1994, 111, 43.

[35] Kikuchi, A.; Nose, T. Macromolecules 1997, 30, 896.

[36] Zhang, M. F.; Breiner, T.; Mori, H.; Müller, A. H. E. Polymer 2003, 44, 1449.

[37] Li, C. H.; Ge, Z. S.; Fang, J.; Liu, S. Y. Macromolecules 2009, 42, 2916.

[38] Yuan, W. Z.; Yuan, J. Y.; Zhang, F. B.; Xie, X. M.; Pan, C. Y. Macromolecules 2007, 40, 9094.

[39] Huang, K.; Rzayev, J. J. Am. Chem. Soc. 2009, 131, 6880.

[40] Yuan, Y. Y.; Du, Q.; Wang, Y. C.; Wang, J. Macromolecules 2010, 43, 1739.

[41] Park, J. H.; Kwon, S.; Nam, J. O. J. Controlled Release 2004, 95, 579.

[42] Gao, Z. G.; Lee, D. H.; Kim, D. I. J. Drug Targeting 2005, 13, 391.

[43] Yoo, H. S.; Park, T. G. J. Controlled Release 2001, 70, 63.

[44] Marin, A.; Sun, H.; Husseini, G. J. Controlled Release 2002, 84, 39.

[45] Yoo, H. S.; Park, T. G. J. Controlled Release 2004, 96, 273.

[46] Wang, C. H.; Hsiue, G. H. J. Controlled Release 2005, 108, 140.

[47] Liu, C. Y.; Hu, J. h.; Yang, D.; Yang, W. L. Acta Chim. Sinica 2009, 67, 843 (in Chinese). (刘聪颖, 胡建华, 杨东, 杨武利, 化学学报, 2009, 67, 843.)

[48] Zheng, X. L.; Ding, A. S.; Luo, D.; Gao, H. S. Acta Chim. Sinica 2012, 70, 92 (in Chinese). (郑兴良, 丁爱顺, 罗丹, 高鸿盛, 化学学报, 2012, 70, 92.)

[49] Yuan, L.; Wang, P. D.; Tang, Q. Q.; Zhang, X. H.; Zhang, X. H.; Yang, D.; Hu, J. H. Chin. J. Org. Chem. 2010, 30, 640 (in Chinese). (袁丽, 王蓓娣, 唐倩倩, 张晓鸿, 张晓环, 杨东, 胡建华, 有机化学, 2010, 30, 640.)

[50] Huang, X. W.; Gu. L. N.; Lu, G. L.; Huang, X.; Zhang, Y. L.; Huang, X. Y. Acta Chim. Sinica 2008, 66, 2653 (in Chinese). (黄晓炜, 顾丽娜, 陆国林, 黄啸, 张亚琴, 黄晓宇, 化学学报, 2008, 66, 2653.)

[51] Huang, X. W.; Gu. L. N.; Lu, G. L.; Huang, X.; Zhang, Y. L.; Huang, X. Y. Acta Chim. Sinica 2009, 67, 1363 (in Chinese). (黄晓炜, 顾丽娜, 陆国林, 黄啸, 张亚琴, 黄晓宇, 化学学报, 2009, 67, 1363.)

[52] Jia, Z. F.; Fu, Q.; Huang, J. L. Macromolecules 2006, 39, 5190

[53] Queffelec, J.; Gaynor, S. G.; Matyjaszewski, K. Macromolecules 2000, 33, 8629.

[54] Cai, C. H.; Wang, L. Q.; Lin, J. P. Chem. Commun. 2011, 47, 11189.

PPEGMEA-g-PBLG两亲性接枝共聚物的合成及其作为阿霉素输送载体的研究

Synthesis of PPEGMEA-g-PBLG Amphiphilic Graft Copolymer and Its Research as Doxorubicin Delivery Vectors

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