Nucleic acid delivery with chitosan and its derivatives

Chitosan is a naturally occurring cationic mucopolysaccharide. It is generally biocompatible, biodegradable, mucoadhesive, non-immunogenic and non-toxic. Although chitosan is able to condense nucleic acids (NA) (both DNA and RNA) and protect them from nuclease degradation, its poor water solubility and low transfection efficacy have impeded its use as an NA carrier. In order to overcome such limitations, a multitude of strategies for chitosan modification and formulation have been proposed. In this article, we will first give a brief overview of the physical and biological properties of chitosan. Then, with a special focus on plasmid DNA delivery, we will have a detailed discussion of the latest advances in chitosan-mediated NA transfer. For future research, the following three important areas will be discussed: chitosan-mediated therapeutic small RNA transfer, structure-activity relationships (SAR) in chitosan vector design, and chitosan-mediated oral/nasal NA therapy. (C) 2008 Elsevier B.V. All rights reserved.