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.