PEG-based Polyplex Design for Gene and Nucleotide Delivery

Gene delivery is a multiple-step process which depends on the ability of a gene carrier to overcome several biological barriers and safely deliver a transgene to its target cells. Polymeric gene delivery systems, e.g., polyplexes, have emerged as a safe alternative to viral vectors. Poly(ethylene glycol) (PEG) conjugation is a common modification approach to provide polyplexes with prolonged circulation time and reduced toxicity, and to allow their accumulation in tumor tissue through the enhanced permeability and retention (EPR) effect. This review describes physicochemical properties related to the biological activity of PEG-based polyplexes, and approaches undertaken to promote a rational design for their in vivo applications.