Polyethylenimine Carriers for Drug and Gene Delivery

Polyethylenimine (PEI) is a cationic polymer with a high density of amine groups suitable for strong electrostatic interactions with biological molecules to preserve their bioactivities during encapsulation and after delivery for biomedical applications. This review provides a comprehensive overview of PEI as a drug and gene carrier, describing its polymerization methods in both linear and branched forms while highlighting the processing methods to manufacture PEIs into drug carriers, such as nanoparticles, coatings, nanofibers, hydrogels, and films. These various PEI carriers enable applications in non-viral gene and small molecule drug deliveries. The structure-property relationships of PEI carriers are discussed with emphasis on how molecular weights, branching degrees, and surface modifications of PEI carriers impact biocompatibility, transfection efficiency, and cellular interactions. While PEI offers remarkable potential for drug and gene delivery, its clinical translation remains limited by challenges, including cytotoxicity, non-degradability, and serum instability. Our aim is to provide an understanding of PEI and the structure-property relationships of its carrier forms to inform future research directions that may enable safe and effective clinical use of PEI carriers for drug and gene delivery.