Can Design, Synthesis And Properties Of New Crosslinked Polyethylene Imine In Vivo Degradation Study

Some multi-hydroxyl cationic polymers for gene delivery systems with good biodegradability and water-solubility were synthesized in this paper, and the gene transfection efficiency of which was also evaluated. polyethylenimine(PEI) has been known as efficient gene carrier with the highest cationic charge potential. High transfection efficiency of PEI, along with its cytotoxicity, stongly depends on its molecular weight. Small PEI is usually non-cytotoxic but less efficient. In order to enhance the water-solubility and minimize cytotoxicity of PEI, We designed and synthesized three polyhydroxylated crosslinkers (LDLT,DMDG,DATD) and two epoxy-based crosslinkers(EGAEP and EGDEP). 89 water-solubility improved polymers were prepared by non-cytotoxic smaller PEI reacting with different potentially biodegradable crosslinkers we have syntesized. The polymers that are soluble in water were assessed when HEK293 cells were used as receptor cell and enhanced green fluorescent protein (EGFP) was used as gene reporter. Then we picked out four new polymers with high transfection efficiency in the products, and the highest GFP positive ratio is 91% among of the four polymers; The transfection efficiency of the four polymers was also investigated in A549 cell, Results showed that their transfection efficiency are 2-5 times more efficient than that of bPEI25kDa, Additionally, these polymers exhibit much lower cytotoxicity than bPEI25kDa in 293 and A549 cells. The four efficient polymers are similar with bPEI25kDa in their condensing DNA into nanoparticles. The results indicated that the biodegradable crosslinked PEIs including hydroxyl have excellent properties for the development of highly potent and nontoxic polymeric gene carriers.