1. Eur J Pharm Biopharm. 2009 Sep;73(1):16-24. Epub 2009 May 4.

Targeting nanoparticles to M cells with non-peptidic ligands for oral
vaccination.

Fievez V, Plapied L, des Rieux A, Pourcelle V, Freichels H, Wascotte V,
Vanderhaeghen ML, Jerôme C, Vanderplasschen A, Marchand-Brynaert J, Schneider YJ,
Préat V.

Université Catholique de Louvain, Unité de Pharmacie Galénique, Brussels,
Belgium.

The presence of RGD on nanoparticles allows the targeting of beta1 integrins at
the apical surface of human M cells and the enhancement of an immune response
after oral immunization. To check the hypothesis that non-peptidic ligands
targeting intestinal M cells or APCs would be more efficient for oral
immunization than RGD, novel non-peptidic and peptidic analogs (RGD
peptidomimitic (RGDp), LDV derivative (LDVd) and LDV peptidomimetic (LDVp)) as
well as mannose were grafted on the PEG chain of PCL-PEG and incorporated in
PLGA-based nanoparticles. RGD and RGDp significantly increased the transport of
nanoparticles across an in vitro model of human M cells as compared to
enterocytes. RGD, LDVp, LDVd and mannose enhanced nanoparticle uptake by
macrophages in vitro. The intraduodenal immunization with RGDp-, LDVd- or
mannose-labeled nanoparticles elicited a higher production of IgG antibodies than
the intramuscular injection of free ovalbumin or intraduodenal administration of 
either non-targeted or RGD-nanoparticles. Targeted formulations were also able to
induce a cellular immune response. In conclusion, the in vitro transport of
nanoparticles, uptake by macrophages and the immune response were positively
influenced by the presence of ligands at the surface of nanoparticles. These
targeted-nanoparticles could thus represent a promising delivery system for oral 
immunization.

PMID: 19409989 [PubMed - in process]