Amphiphilic graft copolymer based on poly(styrene-co-maleic anhydride) with low molecular weight polyethylenimine for efficient gene delivery

Xiaopin Duan,^1,2 Jisheng Xiao,² Qi Yin,² Zhiwen Zhang,² Shirui Mao,¹ Yaping Li<sup>2

1</sup>School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, ²Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

Background and methods: A new amphiphilic comb-shaped copolymer (SP) was synthesized by conjugating poly(styrene-co-maleic anhydride) with low molecular weight polyethyleneimine for gene delivery. Fourier transform infrared spectrum, ¹H nuclear magnetic resonance, and gel permeation chromatography were used to characterize the graft copolymer.
Results: The buffering capability of SP was similar to that of polyethyleneimine within the endosomal pH range. The copolymer could condense DNA effectively to form complexes with a positive charge (13–30 mV) and a small particle size (130–200 nm) at N/P ratios between 5 and 20, and protect DNA from degradation by DNase I. In addition, SP showed much lower cytotoxicity than polyethyleneimine 25,000. Importantly, the gene transfection activity and cellular uptake of SP-DNA complexes were all markedly higher than that of complexes of polyethyleneimine 25,000 and DNA in MCF-7 and MCF-7/ADR cell lines.
Conclusion: This work highlights the promise of SP as a safe and efficient synthetic vector for DNA delivery.

Keywords: poly(styrene-co-maleic anhydride), polyethylenimine, DNA, gene delivery