Synthesis and Characterization of Low Cytotoxicity Polyvinylamine (PVAm)-Based Cationic Polymers

Cationic polymers are the subject of the most extensive investigation among synthetic vehicles because they can form tight complexes with nucleic acids through electrostatic interactions. Polyvinylamine (PVAm) is a polymer with a high content of primary amine functional groups that can ionize to -NH₃⁺ in water, enabling PVAm to be a cationic polymer. However, the high charge density of -NH₃⁺ has strong electrostatic interactions with cell membranes, resulting in cell membrane damage and high cytotoxicity. Therefore, a decrease in cytotoxicity is achieved by designing the relevant chemical modifications including the epoxide ring-opening reaction, amine-carboxylic acid coupling reaction, and amine-ketone reaction on the PVAm backbone to reduce the internal order of the polyplexes. This study investigates how saturated, unsaturated, multi-tails, and hydrogen-bonded tails affect cell cytotoxicity. Additionally, the PVAm-based cationic polymers form mixed micelles with Kolliphor P188. The grafted hydrophobic chains are hypothesized to shield the polymer's positive surface charge, thereby reducing nonspecific electrostatic interactions with cells and mitigating toxicity. This work provides insights and design strategies for developing low-cytotoxicity PVAm-based cationic polymers with potential in nucleic acid delivery applications.