Acid-labile poly(amino alcohol ortho ester) based on low molecular weight polyethyleneimine for gene delivery

A series of acid-labile poly(amino alcohol ortho ester) (POEeis) were synthesized through ring-opening polymerization between diglycidyl ethers with ortho ester bonded and low molecular weight polyethyleneimine by various feed molar ratios. The obtain POEei 1 and POEei 2 exhibited clear kinetic of degradation and condensed plasmid DNA into nanoparticles of suitable sizes (250-300 nm) and positive zeta potentials (+20-30 mV) while protecting DNA from enzymatic digestion. Further, these polymers have uniform distribution of abundant hydroxyl groups, which could improve their water solubility, biocompatibility, and lower protein adsorption. Significantly, ortho ester groups in POEeis main-chains could hydrolyze rapidly at acidic endosomal pH, resulting in intracellular DNA release and diminished material toxicity. MTT assay revealed that all the polymers exhibited much lower cytotoxicity than 25 kDa PEI in the human neuroblastoma SH-SY5Y cells. Moreover, the transfection efficiency of POEei 1 was higher than 25 kDa PEI in serum-free medium or 10% serum medium.