Polymeric micelles have found a growing interest as gene vectors due to the serious safety concerns associated with viral vectors. In particular, the cationic polymer polyethylene imine (PEI) has shown relatively high condensation and transfection efficiencies. Additionally, polyethylene glycol (PEG) modification of polymeric gene vectors has dramatically improved their biological properties, including enhanced biocompatibility, prolonged circulation time, and increased bio-distribution. However, PEG grafting of PEI for subsequent condensation of nucleic acids (NAs) does not necessarily result in the formation of a PEI/NAs core with a PEG corona. But often times, the presence of PEG interferes with PEI's electrostatic interaction with NAs. We describe here a facile method to prepare multilayered biodegradable micelles which address some of the critical drawbacks associated with current PEI-based systems. The polyplex micelles have superb stability and stealth properties. Moreover, we describe a method to prepare fully biodegradable and biocompatible injectable hydrogels for use in localized gene therapy.
Keywords: Biodegradable; Block copolymers; DNA delivery; Hydrogels; Injectable; Micelles; PEG; PEI; PLLA.