Enhancing the Biocompatibility and Biodegradability of Linear Poly(ethylene imine) through Controlled Oxidation

(Bio)degradable poly(ethylene imine-co-glycine)s (P(EI-co-Gly)) were synthesized through efficient and controlled oxidation of linear poly(ethylene imine) (LPEI) using hydrogen peroxide in a methanol/water mixture. Temperature, peroxide concentration, and reaction time were varied to adjust the degree of oxidation (DO). At low temperatures, the oxidation process was found to be well-controlled with almost 85% of ethylene imine units converted to the corresponding amide. Importantly, oxidation of more than 10% of the LPEI rendered the polymers water-soluble. The oxidation reaction and molecular structure of P(EI-co-Gly)s were studied in detail by various nuclear magnetic resonance (NMR) methods, infrared (IR) spectroscopy, and size exclusion chromatography (SEC). The introduction of backbone amide groups to the P(EI-co-Gly)s facilitated its (bio)degradation under acidic conditions or by proteases. Moreover, the P(EI-co-Gly)s exhibited negligible cytotoxicity, particularly relative to LPEI. The interaction of the copolymers with serum-containing medium was investigated showing no indication of coagulation. Preliminary studies indicate that P(EI-co-Gly) is a promising biodegradable polymer with negligible toxicity in human cell lines.