差别性释放两种药物的层层组装聚合物膜

doi:10.7503/cjcu20150683

高等学校化学学报 ›› 2015, Vol. 36 ›› Issue (11): 2342.doi: 10.7503/cjcu20150683

差别性释放两种药物的层层组装聚合物膜

陈栋栋¹, 陈杰², 田华雨², 陈学思², 孙俊奇¹()

1. 吉林大学超分子结构与材料国家重点实验室, 化学学院, 长春 130012
2. 中国科学院生态环境高分子材料重点实验室, 长春应用化学研究所, 长春 130022

收稿日期:2015-09-01 出版日期:2015-11-10 发布日期:2015-10-26
作者简介:联系人简介: 孙俊奇, 男, 博士, 教授, 博士生导师, 主要从事功能性聚合物膜方面的研究. E-mail:sun_junqi@jlu.edu.cn
基金资助:
国家自然科学基金(批准号: 21225419, 21221063)资助

Layer-by-layer Assembled Polymeric Films for Differential Release of Dual Drugs^†

CHEN Dongdong¹, CHEN Jie², TIAN Huayu², CHEN Xuesi², SUN Junqi^1,^*()

1. State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry,Jilin University, Changchun 130012, China
2. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry,Chinese Academy of Sciences, Changchun 130022, China

Received:2015-09-01 Online:2015-11-10 Published:2015-10-26
Contact: SUN Junqi E-mail:sun_junqi@jlu.edu.cn
Supported by:
† Supported by the National Natural Science Foundation of China(Nos.21225419, 21221063)

摘要/Abstract

摘要：

基于层层组装技术制备了能够差别性释放2种药物的聚合物复合膜. 通过大分子前体药物透明质酸-阿霉素(HA-DOX)与壳聚糖(HACC)的层层组装以及膜内后扩散负载甲氨喋呤二钠盐(MTX)的方法, 实现了DOX和MTX 2种药物分子在聚合物膜中的负载. DOX和MTX在癌变组织的酸性环境下具有差别性的释放动力学, MTX在24 h内快速释放, 而DOX长效缓释达10 d. 细胞实验结果表明, 差别性释放的DOX和MTX可有效地抑制癌细胞的增殖.

关键词: 层层组装, 聚合物膜, 药物传递, 差别性释放

Abstract:

Layer-by-layer(LbL)-assembled polymeric films capable of differentially releasing dual anticancer drugs to achieve synergetic therapeutic effects were fabricated. Doxorubicin(DOX) was first conjugated to hyaluronic sodium(HA) via acid labile hydrazone bonds to produce HA-DOX prodrugs. Then HA-DOX was alternately deposited with 2-hydroxypropyltrimethyl ammonium chloride chitosan(HACC) to produce (HACC/HA-DOX)_n(n is the number of deposition cycle) film. Methotrexate(MTX) was then loaded into (HACC/HA-DOX)₂₀ film by a post-diffusion process. MTX was quickly released due to the breakage of its electrostatic interaction with film component HACC. Meanwhile, DOX was released in a sustained manner because of the slow hydrolysis of hydrazine bonds. The synergetic therapeutic effects can be achieved by fast release of cell cycle specific drug MTX to effectively inhibit the proliferation of cancer cells and by sustained release of cell cycle non-specific drug DOX to kill cancer cells. The present study provides a new way for designing polymeric films for controlled release of multiple therapeutic agents.

Key words: Layer-by-layer assembly, Polymeric film, Drug delivery, Differential release

中图分类号:

O631
O636

TrendMD:

陈栋栋, 陈杰, 田华雨, 陈学思, 孙俊奇. 差别性释放两种药物的层层组装聚合物膜. 高等学校化学学报, 2015, 36(11): 2342.

CHEN Dongdong, CHEN Jie, TIAN Huayu, CHEN Xuesi, SUN Junqi. Layer-by-layer Assembled Polymeric Films for Differential Release of Dual Drugs^†. Chem. J. Chinese Universities, 2015, 36(11): 2342.

图/表 6

Fig.1 Chemical structures of MTX(A), DOX(B) and HA-DOX(C)

Fig.2 UV-Vis absorption spectra of HACC/HA-DOX films with different numbers of deposition cycles(1—10) on quartz substrates(A) and the thickness of HACC/HA-DOX films as a function of the number of deposition cycles(B) Inset in (A) shows the absorbance of the films at 480 nm as a function of the number of deposition cycles. Inset in(B) shows the digital photograph of a quartz substrate after deposition of a (HACC/HA-DOX)20 film.

Fig.3 Time-dependent loading profile of MTX into (HACC/HA-DOX)20 film(A) and the digital photograph of a (HACC/HA-DOX)20 film after loading MTX(B)

Fig.4 Time-dependent release profiles of MTX(■) and DOX(●) from MTX-(HACC/HA-DOX)20 film in PBS (A) Release profile in 24 h; (B) release profile in 10 d.

Fig.5 Bright-field(A—C) and fluorescence(D—F) images of HeLa cells incubated with control PBS and released drug solution (A), (D) control PBS; (B), (E) MTX released from the MTX-(HACC/HA)20 film; (C), (F) MTX and DOX released from the MTX-(HACC/HA-DOX)20 film.

Fig.6 Cell viability of HeLa cells incubated with MTX released from the MTX-(HACC/HA)20 film and MTX +DOX released from the MTX-(HACC/HA-DOX)20 film for 12 h(a), 24 h(b) and 48 h(c)

参考文献 41

[1]	Soussan E., Cassel S., Blanzat M., Rico-Lattes I., Angew. Chem. Int. Ed., 2009, 48(2), 274—288
[2]	Timko B. P., Dvir T., Kohane D. S., Adv. Mater., 2010, 22(44), 4925—4943
[3]	He C., Zhuang X., Tang Z., Tian H., Chen X., Adv. Healthcare Mater., 2012, 1(1), 48—78
[4]	Yokoyama M., Expert Opin. Drug Deliv., 2010, 7(2), 145—158
[5]	Akimoto J., Nakayama M., Okano T., J. Control Release, 2014, 193, 2—8
[6]	Ma N., Li Y., Xu H., Wang Z., Zhang X., J. Am. Chem. Soc., 2010, 132(2), 442—443
[7]	Bozzuto G., Molinari A., Int. J. Nanomedicine, 2015, 10, 975—999
[8]	Panyam J., Labhasetwar V., Adv. Drug Deliv. Rev., 2003, 55(3), 329—347
[9]	Cheng R., Meng F., Deng C., Klok H. A., Zhong Z., Biomaterials, 2013, 34(14), 3647—3657
[10]	Wu H., Li J., Wei J., Dai Y., Peng Z., Chen Y., Liu T., Chem. Res. Chinese Universities, 2015, 31(5), 890—894
[11]	Wu W., Shen J., Banerjee P., Zhou S., Biomaterials, 2010, 31(32), 8371—8381
[12]	Qiu Y., Park K., Adv. Drug Deliv. Rev., 2001, 53(3), 321—339
[13]	Freiberg S., Zhu X. X., Int. J. Pharm., 2004, 282(1/2), 1—18
[14]	Becker A. L., Johnston A. P. R., Caruso F., Small, 2010, 6(17), 1836—1852
[15]	Han Y., Bu J., Zhang Y., Tong W., Gao C., Macromol. Biosci., 2012, 12(10), 1436—1442
[16]	Tang Z., Wang Y., Podsiadlo P., Kotov N. A., Adv. Mater., 2006, 18(24), 3203—3224
[17]	Pavlukhina S., Sukhishvili S., Adv. Drug Deliv. Rev., 2011, 63(9), 822—836
[18]	Wang L., Chen D., Sun J., Langmuir, 2009, 25(14), 7990—7994
[19]	Shukla A., Avadhany S. N., Fang J. C., Hammond P. T., Small, 2010, 6(21), 2392—2404
[20]	Chen D., Wu M., Chen J., Zhang C., Pan T., Zhang B., Tian H., Chen X., Sun J., Langmuir, 2014, 30(46), 13898—13906
[21]	Jiao Y. H., Li Y., Wang S., Zhang K., Jia Y. G., Fu Y., Langmuir, 2010, 26(11), 8270—8273
[22]	Cao W., Wang L., Xu H., Chem. Commun., 2015, 51(25), 5520—5522
[23]	Zhang H., Wang G., Yang H., Expert Opin. Drug Deliv., 2011, 8(2), 171—190
[24]	Zeng L., Hu J., Wei J.G.,Chem. J. Chinese Universities, 2014, 35(8), 1788—1794
	(曾莉, 胡俊, 魏俊超. 高等学校化学学报, 2014, 35(8), 1788—1794)
[25]	Godsey M. E., Suryaprakash S., Leong K. W., RSC Adv., 2013, 3(47), 24794—24811
[26]	Wang L., Wang X., Xu M., Chen D., Sun J., Langmuir, 2008, 26(11), 8187—8194
[27]	Thierry B., Kujawa P., Tkaczyk C., Winnik F. M., Bilodeau L., Tabrizian M., J. Am. Chem. Soc., 2005, 127(6), 1626—1627
[28]	Dierich A., Le Guen E., Messaddeq N., Stoltz J. F., Netter P., Schaaf P., Voegel J. C., Benkirane-Jessel N., Adv. Mater., 2007, 19(5), 693—697
[29]	Berg M. C., Zhai L., Cohen R. E., Rubner M. F., Biomacromolecules, 2006, 7(1), 357—364
[30]	Smith R. C., Riollano M., Leung A., Hammond P. T., Angew. Chem. Int. Ed., 2009, 48(47), 8974—8977
[31]	Serpe M.J., Yarmey K. A., Nolan C. M., Lyon L.A., Biomacromolecules, 2005, 6(1), 408—413
[32]	Saurer E. M., Jewell C. M., Roenneburg D. A., Bechler S. L., Torrealba J. R., Hacker T. A., Lynn D. M., Biomacromolecules, 2013, 14(5), 1696—1704
[33]	Cai S., Thati S., Bagby T. R., Diab H. M., Davies N. M., Cohen M. S., Forrest M. L., J. Control Release, 2010, 146(2), 212—218
[34]	Denny W. A., Eur. J. Med. Chem., 2001, 36(7/8), 577—595
[35]	Wang H., Xu F., Li D., Liu X., Jin Q., Ji J., Polym. Chem., 2013, 4(6), 2004—2010
[36]	Guo H., Yang C. L., Wang W., Lai Q. Y., Yuan Z., Chem. J. Chinese Universities, 2014, 35(8), 1835—1842
	(郭华, 杨承玲, 王蔚, 赖全勇, 袁直. 高等学校化学学报, 2014, 35(8), 1835—1842)
[37]	Picart C., Mutterer J., Richert L., Luo Y., Prestwich G. D., Schaaf P., Voegel J. C., Lavalle P., Proc. Natl. Acad. Sci. USA, 2002, 99(20), 12531—12535
[38]	Chen D. D., Wang L., Sun J. Q., Acta Chim. Sinica, 2012, 70(17), 1779—1784
	(陈栋栋, 王林, 孙俊奇. 化学学报, 2012, 70(17), 1779—1784)
[39]	Porcel C., Lavalle P., Ball V., Decher G., Senger B., Voegel J. C., Schaaf P., Langmuir, 2006, 22(9), 4376—4383
[40]	Zhou Y., Cheng M., Zhu X., Zhang Y., An Q., Shi F., ACS Appl. Mater. Interfaces, 2013, 5(17), 8308—8313
[41]	Wang Y., An Q., Zhou Y., Niu Y., Akram R., Zhang Y., Shi F., J. Mater. Chem. B, 2015, 3, 562—569

差别性释放两种药物的层层组装聚合物膜

Layer-by-layer Assembled Polymeric Films for Differential Release of Dual Drugs^†

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差别性释放两种药物的层层组装聚合物膜

Layer-by-layer Assembled Polymeric Films for Differential Release of Dual Drugs†

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Layer-by-layer Assembled Polymeric Films for Differential Release of Dual Drugs^†