[en] The presence of RGD on nanoparticles allows the targeting of β1 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.
Research Center/Unit :
Center for Education and Research on Macromolecules (CERM)
Disciplines :
Chemistry Materials science & engineering
Author, co-author :
Fievez, Virginie; Université catholique de Louvain (UCL) > Unité de Pharmacie Galénique (Bruxelles) et Laboratoire de Biochimie cellulaire, toxicologique et nutritionnelle (Louvain-la-Neuve)
Plapied, Laurence; Université catholique de Louvain (UCL),Bruxelles > Unité de Pharmacie Galénique
des Rieux, Anne; Université catholique de Louvain (UCL), Bruxelles > Unité de Pharmacie Galénique
Pourcelle, Vincent; Université catholique de Louvain (UCL) > Unité de Chimie Organique et Médicinale
Freichels, Hélène; Université de Liège - ULiège > Department of Chemistry > Center for Education and Research on Macromolecules (CERM)
Wascotte, Valentine; Université catholique de Louvain (UCL), Bruxelles > Unité de Pharamcie Galénique
Vanderhaegen, Marie-Lyse; Université catholique de Louvain (UCL), Bruxelles > Unité de Pharamcie Galénique
Jérôme, Christine ; Université de Liège - ULiège > Department of Chemistry > Center for Education and Research on Macromolecules (CERM)
Vanderplasschen, Alain ; Université de Liège - ULiège > Département des Maladies infectieuses et parasitaires > Immunologie et vaccinologie
Marchand-Brynaert, Jacqueline; Université catholique de Louvain (UCL) > Unité de Chimie Organique et Médicinale
Préat, Véronique; Université catholique de Louvain (UCL), Bruxelles > Unité de Pharmacie Galénique
Language :
English
Title :
Targeting nanoparticles to M cells with non-peptidic ligands for oral vaccination
Publication date :
2009
Journal title :
European Journal of Pharmaceutics and Biopharmaceutics
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