PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination.
To improve the efficiency of orally delivered vaccines, PEGylated PLGA-based nanoparticles displaying RGD molecules at their surface were designed to target human M cells. RGD grafting was performed by an original method called "photografting" which covalently linked RGD peptides mainly on the PEG moiety of the PCL-PEG, included in the formulation. First, three non-targeted formulations with size and zeta potential adapted to M cell uptake and stable in gastro-intestinal fluids, were developed. Their transport by an in vitro model of the human Follicle associated epithelium (co-cultures) was largely increased as compared to mono-cultures (Caco-2 cells). RGD-labelling of nanoparticles significantly increased their transport by co-cultures, due to interactions between the RGD ligand and the beta(1) intregrins detected at the apical surface of co-cultures. In vivo studies demonstrated that RGD-labelled nanoparticles particularly concentrated in M cells. Finally, ovalbumin-loaded nanoparticles were orally administrated to mice and induced an IgG response, attesting antigen ability to elicit an immune response after oral delivery.
Garinot
Marie
M
Université Catholique de Louvain, Unité de Pharmacie Galénique, Brussels, Belgium.
Fiévez
Virginie
V
Pourcelle
Vincent
V
Stoffelbach
François
F
des Rieux
Anne
A
Plapied
Laurence
L
Theate
Ivan
I
Freichels
Hélène
H
Jérôme
Christine
C
Marchand-Brynaert
Jacqueline
J
Schneider
Yves-Jacques
YJ
Préat
Véronique
V
D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D039081:Integrin alpha5beta1 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008815:Mice, Inbred Strains; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000378:metabolism; D010047:Ovalbumin / Q000493:pharmacokinetics / Q000494:pharmacology; D006080:Ovarian Follicle / Q000166:cytology; D010581:Peyer's Patches / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D014611:Vaccination / Q000379:methods*
D039081:Integrin alpha5beta1; D019012:Integrin beta1; D009842:Oligopeptides; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D010047:Ovalbumin; D016650:Fluorescein-5-isothiocyanate