Development of chitosan microsphere for a nasal vaccine delivery system

Abstract

The potential to generate both systemic and local immune response makes the mucosal system as an attractive site for immunization. However, mucosal administration of protein and peptide antigens generally results in a poor immune response. Therefore, successful mucosal vaccination is largely dependent on the development of effective mucosal adjuvants. In this study, chitosan microspheres (CMs) and pegylated chitosan microspheres (PCMs) were prepared by ionic gelation process with tripolyphosphate (TPP). Bordetella Bronchiseptica Dermonecrotoxin (BBD) as a major virulence factor of a causative agent of atrophic rhinitis (AR) was loaded to the CMs (or PCMs) for nasal vaccination. BBD-loaded CMs (or BBD-loaded PCMs) were observed as aggregated shapes although unloaded CMs (or PCMs) were observed as relatively spherical ones. The average particle sizes of the BBD-loaded CMs and BBD-loaded PCMs were 4.39 and 5.47 ¥ìm, respectively. The lower molecular weight of chitosan and the higher medium pH, the more release of BBD from the BBD-loaded CMs was observed in vitro due to weaker intermolecular interaction between chitosan and BBD. More BBD was released from BBD-loaded PCMs than BBD-loaded CMs, and more mechanically stabilized BBD-loaded PCMs were obtained than BBD-loaded CMs. Tumor necrosis factor ¥á (TNF-¥á) and nitric oxide (NO) from RAW264.7 cells stimulated with BBD-loaded CMs (or BBD-loaded PCMs) were gradually secreted, suggesting that BBD released from BBD-loaded CMs (or BBD-loaded PCMs) has a long-lasting boosting effect and CMs (or PCMs) are very promising vaccine delivery system.