Polymers including poly(amine-co-ester), poly(amine-co-amide), or a combination thereof, and nanoparticles, particularly solid core nanoparticles, formed therefrom are provided. Solid core nanoparticles fabricated from hydrophobic polymers often require the presence of cationic complexing agents to stabilize negatively charged active agents such as siRNA. However, complexing agents are optional in the disclosed formulations because the nanoparticles contain cationic amines to stabilize negatively charged nucleic acids and hydrophobic domains to condense the nucleic acid into the core of the formed nanoparticles, thus improving encapsulation efficiency. This increase in nucleic acid loading allows the disclosed solid core nanoparticles to deliver more nucleic acid per cell without increasing total polymer delivered, further reducing cytotoxicity. Pharmaceutical compositions including an effective amount of the nanoparticles are also provided, and be used, for example, for in vitro and in vivo delivery of nucleic acids.
