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

doi:10.7503/cjcu20150683

Abstract

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

CLC Number:

O631
O636

TrendMD:

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

Figures/Tables 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)

References 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