The effect of N/P ratio on the in vitro and in vivo interaction properties of PEGylated poly[2-(dimethylamino)ethyl methacrylate]-based siRNA complexes.

PEG-PnBA-PDMAEMA triblock and PEG-PDMAEMA diblock copolymers are used as model systems for studying the role of N/P ratio on the in vivo behavior of PEGylated siRNA carriers in mice. The presence of a free/uncomplexed polymer population coexisting with siRNA complexes is established. A change in the N/P ratio exerts no significant influence on the in vivo biodistribution and ex vivo blood chemistry properties of the respective systems.

Influence of nano-carrier architecture on in vitro siRNA delivery performance and in vivo biodistribution: polyplexes vs micelleplexes.

Micelle-based siRNA carriers ("micelleplexes") were prepared from the A-B-C triblock copolymer poly(ethylene glycol)-poly(n-butyl acrylate)-poly(2-(dimethylamino)ethyl methacrylate) (PEG-PnBA-PDMAEMA), and their in vitro performance and in vivo biodistribution properties were compared with the benchmark PEGylated and basic polycation systems PEG-PDMAEMA and PDMAEMA, respectively. The micelle architecture, incorporating increased PEG shielding and a larger particle size (∼50 nm) than polycation-based complexes (polyplexes; ∼10 nm), enhances siRNA delivery performance in two important aspects: in vitro gene silencing efficiency and in vivo tumor accumulation. The in vitro gene silencing efficiency of the micelleplexes (24% in HeLa cells) was significantly better than the statistically insignificant levels observed for PDMAEMA and PEG-PDMAEMA polyplexes under identical conditions.

Polymer-based siRNA delivery: perspectives on the fundamental and phenomenological distinctions from polymer-based DNA delivery.

Gene therapy holds tremendous promise in the treatment of many genetic and acquired diseases. The future of gene therapy in humans, however, is contingent upon the discovery of safe and effective carriers of genetic material. Polymers represent a class of materials that can be extensively modified to meet the needs of a particular gene delivery system.