Investigation of the degradation mechanism of cross-linked polyethyleneimine by NMR spectroscopy

The degradation pathway of a cross-linked polyethyleneimine (c-PEI) suitable as a gene carrier was studied at different pH values by real-time 1H NMR and diffusion-weighted 1H NMR spectroscopy. The c-PEI was synthesized by cross-linking PEI segments with 2,4-pentanediol diacrylate (PDDA). The experimental results show that under basic, neutral and acidic conditions, the degradation of c-PEI occurs through hydrolysis of the ester moieties of the PDDA linkers. The degradation half-life of the polymer is 22, 48 and more than 720 h at pH 10.2, 7.4 and 4.6, respectively, showing that the degradation of c-PEI is highly pH sensitive. By using a modified version of diffusion-weighted 1H NMR experiment, the variation of the apparent molecular weight of c-PEI in the degradation process was monitored. Furthermore, a Monte Carlo simulation was applied to simulate the relation between the average molecular weight and the number of chain ends during the degradation process of a model system of c-PEI. By comparing the NMR results with those obtained from simulation, the mechanism of degradation under various pH conditions is discussed. The present work demonstrates that the combination of real-time 1H NMR, diffusion-weighted 1H NMR spectroscopy and Monte Carlo simulation is a useful strategy for characterizing the degradation process of degradable polymers.