Disulfide-crosslinked poly(L-glutamic acid) grafted mesoporous silica nanoparticles and their potential application in drug delivery

Abstract

Poly(L-glutamic acid)(PLGA) was grafted onto the surface of mesoporous silica nanoparticles(MSN) via the ring opening polymerization of γ-benzyl-L-glutamate N-carboxyanhydride(BLG-NCA) and its subsequent deprotection of benzyl groups. The PLGA chains were cross-linked with cystamine, and thus forming a type of redox responsive drug delivery system(MSN-cPLGA). The structures were characterized by Fourier transform infrared spectrometry(FTIR), transmission electron microscopy(TEM) and energy disperse spectrometry(EDS), demonstrating that disulfide groups existed on the surfaces of MSN-cPLGA particles. The thermal gravimetric analysis(TGA) results show that the PLGA mass fraction is about 33.4% in the MSN-cPLGA hybrid. The in vitro drug release experiments showed that the MSN-cPLGA hybrid can realize the controlled release of model drugs(5-fluorouracil) in response to redox environment. Even 0.1 mmol/L dithiothreitol(DTT) can accelerate the drug release speed, and a concentration of 10.0 mmol/L DTT is higher enough to trigger the open of cross-linked PLGA network so as to realize rapid release of drugs. All the results demonstrate that the cross-linked PLGA chains on the surface of MSN could act as efficient gatekeepers to control the on-off of the pores, showing potential application in drug delivery system.

Keywords

Mesoporous silica nanoparticle / Redox responsive / Drug delivery / Surface modification / Hybrid

References

[1] Lu J., Liong M., Li Z. X., Zink J. I., Tamanoi F. Small, 2010, 6(16): 1794.

[2] Meng H. A., Xue M., Xia T. A., Zhao Y. L., Tamanoi F., Stoddart J. F., Zink J. I., Nel A. E. J. Am. Chem. Soc., 2010, 132: 12690.

[3] He Q. J., Shi J. L. J. Mater. Chem., 2011, 21(16): 5845.

[4] Yang Y. W., Sun Y. L., Song N. Acc. Chem. Res., 2014, 47: 1950.

[5] Sun Y. L., Yang Y. W., Wu W., Zhang S. X. A. Chem. J. Chinese Universities, 2012, 33(8): 1635.

[6] Li Q. L., Sun Y. F., Sun Y. L., Wen J. J., Zhou Y., Bing Q. M., Isaacs L. D., Jin Y. H., Gao H., Yang Y. W. Chem. Mater., 2014, 26: 6418.

[7] Schlossbauer A., Warncke S., Gramlich P. M. E., Kecht J., Manetto A., Carell T., Bein T. Angew. Chem. Int. Ed., 2010, 49(28): 4734.

[8] Coll C., Mondragon L., Martinez-Manez R., Sancenon F., Marcos M. D., Soto J., Amoros P., Perez-Paya E. Angew. Chem. Int. Ed., 2011, 50(9): 2138.

[9] Li Q. L., Wang L. Z., Qiu X. L., Sun Y. L., Wang P. X., Liu Y., Li F., Qi A. D., Gao H., Yang Y. W. Polym. Chem., 2014, 5: 3389.

[10] Sun Y. F., Sun Y. L., Wang L. Z., Ma J. B., Yang Y. W., Gao H. Micropor. Mesopor. Mat., 2014, 185: 245.

[11] Liu R., Zhang Y., Zhao X., Agarwal A., Mueller L. J., Feng P. Y. J. Am. Chem. Soc., 2010, 132(5): 1500.

[12] Yang Y. W. Med. Chem. Commun., 2011, 2: 1033.

[13] Song N., Yang Y. W. Chem. Soc. Rev., 2015, 44: 3474.

[14] Deng C., Jiang Y. J., Cheng R., Meng F. H., Zhong Z. Y. Nano Today, 2012, 7: 467.

[15] Huo M., Yuan J. Y., Tao L., Wei Y. Polym. Chem., 2014, 5: 1519.

[16] Luo Z., Cai K., Hu Y., Zhao L., Liu P., Duan L., Yang W. Angew. Chem. Int. Ed., 2011, l50: 640.

[17] Liu R., Zhao X., Wu T., Feng P. Y. J. Am. Chem. Soc., 2008, 130(44): 14418.

[18] Zhang J., Yuan Z. F., Wang Y., Chen W. H., Luo G. F., Cheng S. X., Zhuo R. X., Zhang X. Z. J. Am. Chem. Soc., 2013, 135(13): 5068.

[19] Yang Y. N., Cai J., Zhuang X. L., Guo Z. P., Jing X. B., Chen X. S. Polymer, 2010, 51(12): 2676.

[20] Wei J. C., Liu A. X., Chen L., Zhang P. B., Chen X. S., Jing X. B. Macromol. Biosci., 2009, 9(7): 631.

[21] Slowing I. I., Trewyn B. G., Giri S., Lin V. S. Y. Adv. Funct. Mater., 2007, 17(8): 1225.

[22] Kar M., Pauline M., Sharma K., Kumaraswamy G., Sen G. S. Langmuir, 2011, 27(19): 12124.

[23] Chang J. S., Kong Z. L., Hwang D. F., Chang K. L. B. Chem. Mater., 2006, 18(3): 702.

[24] Zheng J., Tian X. J., Sun Y. F., Lu D., Yang W. L. Int. J. Pharmaceut., 2013, 450: 296.