Multi-armed poly(L-glutamic acid)-graft-polypropyleneinime as effective and serum resistant gene delivery vectors

作者:Zhang, Xuan*; Hu, Haimei; Liu, Tiebang; Yang, Yeya; Peng, Yuefeng; Cai, Qingqing; Fang, Lijing
来源:International Journal of Pharmaceutics, 2014, 465(1-2): 444-454.
DOI:10.1016/j.ijpharm.2014.02.041

摘要

A new series of multi-armed MP-g-PPI dendrimers were synthesized by polymerization of BLG-NCA using G2.0PPI as macromolecular initiator and subsequent aminolysis with Gl.OPPI or G2.0PPI. The chemical structure and composition of the MP-g-PPI dendrimers were characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (H-1 NMR). The MP-g-PPI showed a great ability to combine with pDNA to form complexes, which protect the pDNA from nuclease degradation. Dynamic light scattering (DLS) measurement illustrated that the sizes of complexes were in range of 111-219 nm. The transmission electron microscope (TEM) and atomic force microscope (AFM) observation showed that the morphology of these complexes was spherical. The MTT assay demonstrated that cytotoxicity of the MP-g-PPI was lower than that of PEI 25K. The in vitro transfection test indicated that MP-g-PPI gene vectors displayed relative high transfection efficiency than that of PEI 25 K and Lipofectamine 2000 in serum-containing medium. Furthermore, MP-g-PPI at the weight ratio of 7.5 displayed better serum-resistant capability than that of PEI 25K and Lipofectamine 2000. The above facts revealed that multi-armed MP-g-PPI dendrimers may be promising gene vectors with low cytotoxicity, high transfection efficiency and serum-resistant ability.