Synthesis and characterization of the novel transfection reagent poly(amino ester glycol urethane)

Poly(ester urethane) (PEU) is a class of biodegradable polymer that has been applied as tissue-engineering scaffolds with minimum toxicity. Despite its unique biocompatibility, there have been no reports in modifying the PEU backbone to design a soluble, PEU-based DNA carrier. We have developed a method of incorporating tertiary amines and poly(ethylene glycol) (PEG) into PEU to synthesize a soluble poly(amino ester glycol urethane) (PaEGU) as a novel transfection reagent. Parallel to this, we have synthesized poly(amino ester) (PaE) and poly(amino ester urethane) (PaEU) as the control polymers. The test transfection reagent PaEGU and the control PaE were similar in their properties of being soluble and buffering pH in water and their capabilities of self-assembling with DNA and transfecting the target cells. Significantly, PaEGU exhibited faster hydrolysis kinetics than PaE, half-lives of 19 and 36 h for PaEGU and PaE, respectively, underlying PaEGU's unique property of low cytotoxicity. However, in comparison to PaEGU, the other control polymer, PaEU, was not readily dissolved in water, indicating the importance of PEG units in PaEGU in increasing polymer hydrophilicity. This study demonstrated a useful synthesis scheme for the PEU-based transfection reagent PaEGU. The combination of tertiary amine, ester, PEG, and urethane units in the polymer backbone constitutes a feasible approach for the future design of low-toxicity gene transfer vectors.