Enhanced Nasal Mucosal Delivery and Immunogenicity of Anti-Caries DNA Vaccine through Incorporation of Anionic Liposomes in Chitosan/DNA Complexes

Abstract

The design of optimized nanoparticles offers a promising strategy to enable DNA vaccines to cross various physiological barriers for eliciting a specific and protective mucosal immunity via intranasal administration. Here, we reported a new designed nanoparticle system through incorporating anionic liposomes (AL) into chitosan/DNA (CS/DNA) complexes. With enhanced cellular uptake, the constructed AL/CS/DNA nanoparticles can deliver the anti-caries DNA vaccine pGJA-P/VAX into nasal mucosa. TEM results showed the AL/CS/DNA had a spherical structure. High DNA loading ability and effective DNA protection against nuclease were proved by gel electrophoresis. The surface charge of the AL/CS/DNA depended strongly on pH environment, enabling the intracellular release of loaded DNA via a pH-mediated manner. In comparison to the traditional CS/DNA system, our new design rendered a higher transfection efficiency and longer residence time of the AL/CS/DNA at nasal mucosal surface. These outstanding features enable the AL/CS/DNA to induce a significantly (p<0.01) higher level of secretory IgA (SIgA) than the CS/DNA in animal study, and a longer-term mucosal immunity. On the other hand, the AL/CS/DNA exhibited minimal cytotoxicity. These results suggest that the developed nanoparticles offer a potential platform for DNA vaccine packaging and delivery for more efficient elicitation of mucosal immunity.

Nanotechnology in dentistry: prevention, diagnosis, and therapy

“…88,89 DNA vaccines, however, have poor immunogenicity in large animals and human beings. Nanotechnology has been employed to tailor delivery vehicles (eg, anionic liposomes in chitosan/DNA nanoparticle complex was used as a delivery vehicle 90 ) to enhance the immunogenicity of anticaries DNA vaccine. Furthermore, the surface charge of the delivery vehicle could be pH dependent to enable the release of the vaccine in a pH-dependent manner.…”

“…Furthermore, the surface charge of the delivery vehicle could be pH dependent to enable the release of the vaccine in a pH-dependent manner. 90 Despite the advances in nanotechnology, its clinical application for caries therapy is not yet feasible. Although, the Ca 2+ -and PO 4 3--releasing nanocomposites have load-bearing capability, their mechanical behavior as Ca 2+ and PO 4 3-ions being released is difficult to estimate and control under identical clinical situations.…”

Multidynamic Liposomes in Nanomedicine: Technology, Biology, Applications, and Disease Targeting

“…9.1a, b) with high-entrapment efficiency with increased therapeutic index, narrow particle size distribution, long-term stability via encapsulation, site avoidance effect with reduced elimination, selective passive targeting to tumor tissues (liposomal DOX), and target-specific active drug loading property. Due to the differences in preparation methods and lipid composition, liposomes were [5][6][7][8][9] classified according to their lamellarity (uni-and multi-lamellar vesicles, MLV), intermediate, or large; and surface charge (anionic, cationic, or neutral) ( Fig. 9.2).…”

“…The pH-dependant surface charge of the AL/CS/DNA enabled the intracellular release of loaded DNA with higher transfection efficiency and longer residence time at nasal mucosal surface. An AL/CS/DNA unique structural feature helps to significantly induce higher level of secretory IgA imposing a long term mucosal immunity and minimal cytotoxicity thereby enabling efficient elicitation of mucosal immunity mediated by improved DNA vaccine packaging and delivery nanoliposomes [2,9].…”

Effects of soybean milk, chitosan, and anti-Streptococcus mutans IgY in malnourished rats’ dental biofilm and the IgY persistency in saliva

“…RISKESDAS stated that, in 2007, caries prevalence in Indonesia is 46.5% [7]. There have been various eff orts that were attempted in preventing carries, including through active and passive immunization [8][9][10][11][12][13]. Recently, passive immunization and anti-microbial substances are the two things that are mostly utilized for the development of caries vaccines [14][15][16][17].…”