Chitosan-based nanoparticles for topical genetic immunization

Numerous studies have reported the prophylactic and therapeutic use of gene tic vaccines for combating a variety of infectious diseases in animal model s. Recent human clinical studies with the gene gun have validated the conce pt of direct targeting of dendritic cells (Langerhan's cells) in the viable epidermis of the skin. However, it is unclear whether the gene gun technol ogy or other needle-free devices will become commercially viable. The objec tive of our studies was to investigate the topical application of chitosan- based nanoparticles containing plasmid DNA (pDNA) as a potential approach t o genetic immunization. Two types of nanoparticles were investigated: (i) p DNA-condensed chitosan nanoparticles, and (ii) pDNA-coated on preformed cat ionic chitosan/carboxymethylcellulose (CMC) nanoparticles. These studies sh owed that both chitosan and a chitosan oligomer can complex CMC to form sta ble cationic nanoparticles for subsequent pDNA coating. Selected pDNA-coate d nanoparticles (with pDNA up to 400 mug/ml) were stable to challenge with serum. Several different chitosan-based nanoparticles containing pDNA resul ted in both detectable and quantifiable levels of luciferase expression in mouse skin 24 h after topical application, and significant antigen-specific IgG Liter to expressed beta -galactosidase at 28 days. (C) 2001 Elsevier S cience B.V. All rights reserved.