1. J Control Release. 2009 Sep 1;138(2):113-21. Epub 2009 May 13.

Mechanistic study of the adjuvant effect of biodegradable nanoparticles in
mucosal vaccination.

Slütter B, Plapied L, Fievez V, Sande MA, des Rieux A, Schneider YJ, Van Riet E, 
Jiskoot W, Préat V.

Leiden/Amsterdam Center for Drug Research, Division of Drug Delivery Technology, 
Einsteinweg 55, 2333 CC Leiden, The Netherlands.

Comment in:
    J Control Release. 2009 Sep 1;138(2):89.

For oral vaccination, incorporation of antigens into nanoparticles has been shown
to protect the antigen from degradation, but may also increase its uptake through
the intestinal epithelium via M-cells. The aim of this study was to understand
the mechanisms by which oral administration of antigen-loaded nanoparticles
induces an immune response and to analyze the effect of the nanoparticle
composition on these mechanisms. Nanoparticles made from chitosan (CS) and its
N-trimethylated derivative, TMC, loaded with a model antigen ovalbumin (OVA) were
prepared by ionic gelation with tripolyphosphate. Intraduodenal vaccination with 
OVA-loaded nanoparticles led to significantly higher antibody responses than
immunization with OVA alone. TMC nanoparticles induced anti-OVA antibodies after 
only a priming dose. To explain these results, the interaction of nanoparticles
with the intestinal epithelium was explored, in vitro, using a follicle
associated epithelium model and visualized, ex vivo, using confocal laser
scanning microscopy. The transport of FITC-OVA-loaded TMC nanoparticles by Caco-2
cells or follicle associated epithelium model was higher than FITC-OVA-loaded CS 
or PLGA nanoparticles. The association of nanoparticles with human monocyte
derived dendritic cells and their effect on their maturation were determined with
flow cytometry. TMC nanoparticles but not CS or PLGA nanoparticles had intrinsic 
adjuvant effect on DCs. In conclusion, depending on their composition,
nanoparticles can increase the M-cell dependent uptake and enhance the
association of the antigen with DC. In this respect, TMC nanoparticles are a
promising strategy for oral vaccination.

PMID: 19445980 [PubMed - in process]