Development of Excipient-Free Freeze-Dryable Unimolecular Hyperstar Polymers for Efficient siRNA Silencing.

We designed a unimolecular hyperstar polymer for efficient small interfering RNA (siRNA) delivery that can be processed under repeated lyophilization and reconstitution without the need of any excipient. The hyperstar polymer contains a biodegradable hyperbranched core and is bound to siRNA through its thousands of cationic arms that radiate from its core. The siRNA/hyperstar complexes showed siRNA transfection efficiency that was superior to that of Lipofectamine2000 in regard to the gene for human Cu, Zn superoxide dismutase 1 (SOD1), whose mutation causes familial amyotrophic lateral sclerosis. More importantly, hyperstar polymers as unimolecular containers minimized the multipolymer cross-interaction during lyophilization, and this maintained the uniquely high transfection efficiency of the siRNA/hyperstar complexes after repeated freeze-drying and reconstitution without the conventional need for excipient.