Targeting nanoparticles to M cells with non-peptidic ligands for oral vaccination.
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.
Fievez
Virginie
V
Université Catholique de Louvain, Unité de Pharmacie Galénique, Brussels, Belgium.
Plapied
Laurence
L
des Rieux
Anne
A
Pourcelle
Vincent
V
Freichels
Hélène
H
Wascotte
Valentine
V
Vanderhaeghen
Marie-Lyse
ML
Jerôme
Christine
C
Vanderplasschen
Alain
A
Marchand-Brynaert
Jacqueline
J
Schneider
Yves-Jacques
YJ
Préat
Véronique
V
D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism; D008024:Ligands; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009842:Oligopeptides / Q000008:administration & dosage / Q000378:metabolism; D014611:Vaccination / Q000379:methods*
D008024:Ligands; D009842:Oligopeptides; C049554:glycyl-arginyl-glycyl-aspartyl-serine