Chitosan is a natural cationic linear polymer that has recently emerged as an alternative nonviral gene delivery system. We have established the relationships between the structure and the properties of chitosan-pDNA polyplexes in vitro. Further, we have compared polyplexes of ultrapure chitosan (UPC) of preferred molecular structure with those of optimised polyethylenimine (PEI) polyplexes in vitro and after intratracheal administration to mice in vivo. Chitosans in which over two out of three monomer units carried a primary amino group formed stable colloidal polyplexes with pDNA. Optimized UPC and PEI polyplexes protected the pDNA from serum degradation to approximately the same degree, and they gave a comparable maximal transgene expression in 293 cells. In contrast to PEI, UPC was non toxic at escalating doses. After intratracheal administration,

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Chitosan oligomers form complexes with DNA in a structure-dependent manner. We conclude that the 24-mer, which has more desirable physical properties than UPC, is more attractive as a gene delivery system than the conventional high molecular weight chitosans.

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At present, there is considerable excitement within the nanotechnology field with regard to the potential use of nanosystems as carriers for mucosal vaccine delivery. Indeed, many of the vaccines available, including protein antigens and DNA vaccines, are very unstable and need to be protected from degradation in the biologic environment. In addition, their efficacy is limited by their poor capacity to cross biologic barriers and reach the target sites. As a consequence, the design of appropriate antigen carriers that could help overcome these problems has become a significant challenge. The goal of the present article is to review the recent advances in the design of polymeric nanosystems intended to be used as carriers for nasal vaccine delivery. More specifically, the authors present nanocarriers that have been made of safe materials, such as biodegradable polyesters and polysaccharides. The information accumulated regarding the in vivo behavior of these nanocarriers indicates that they are able to facilitate the transport of the associated antigen across the nasal epithelium, thus leading to efficient antigen presentation to the immune system. Furthermore, the results suggest that not only the size and surface properties but also the polymer composition and the structural architecture of the nanosystems are critical for the optimization of these antigen carriers. In conclusion, future studies intended to provide increased knowledge regarding these properties and how they relate to the efficiency of the immune responses, will undoubtedly affect the design of new and more effective nasal vaccine delivery strategies.