Poly(amine-co-ester) polymers, methods of forming
active agent-load polyplexes and particles therefrom, and methods of using them for delivery of
nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and / or hydroxyl groups, and methods of making Typically, the compositions are less toxic, more efficient at
drug delivery, or a combination thereof compared to a control other
transfection reagents. In some embodiments, the compositions are suitable for
in vivo delivery, and can be administered systemically to a subject to treat a
disease or condition.