title: Functionalisation of allergen-loaded microspheres with wheat germ agglutinin for targeting enterocytes.
abstract: In this study, we constructed particles applicable for oral immunotherapy of type I allergy by protecting allergens from digestion and supporting intestinal antigen uptake. Therefore, birch-pollen allergens were entrapped in poly(d,l-lactic-co-glycolic acid) microspheres by spray-drying rendering microspheres with a main population of 1-3microm. Microspheres were further coated with wheat germ agglutinin (WGA) to target enterocytes. Coating with WGA did not alter the surface characteristics of the microspheres as demonstrated in scanning electron microscopy. Binding of WGA was specific and could be inhibited by chitotriose to 14.7+/-6.9%. Comparable amounts of allergen were released from both particle-types with 46.3+/-1.7% and 44.5+/-2.6% during 21 days. Simulating gastric digestion in vitro, antigenicity of allergens entrapped in WGA-microspheres was preserved to 59.8+/-1.5% even after 2h. Feedings of BALB/c mice with WGA-microspheres induced higher levels of allergen-specific IgG-levels than gavages of uncoated microparticles or naked protein. Thus, we conclude that WGA-microspheres are suitable vehicles for oral delivery and mucosal targeting due to lectin-mediated bioadhesion.
authors.affiliation: Department of Pathophysiology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria.
authors.forename: Franziska
authors.initials: F
authors.lastname: Walter
authors.forename: Isabella
authors.initials: I
authors.lastname: Schöll
authors.forename: Eva
authors.initials: E
authors.lastname: Untersmayr
authors.forename: Adolf
authors.initials: A
authors.lastname: Ellinger
authors.forename: George
authors.initials: G
authors.lastname: Boltz-Nitulescu
authors.forename: Otto
authors.initials: O
authors.lastname: Scheiner
authors.forename: Franz
authors.initials: F
authors.lastname: Gabor
authors.forename: Erika
authors.initials: E
authors.lastname: Jensen-Jarolim
mesh_terms: D000485:Allergens / Q000737:chemistry*; D000818:Animals; D029662:Betula; D001672:Biocompatible Materials; D018938:Caco-2 Cells; D002241:Carbohydrates / Q000737:chemistry; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020895:Enterocytes / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019793:Fluorescein / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007167:Immunotherapy; D019344:Lactic Acid / Q000737:chemistry; D037102:Lectins / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D037121:Plant Lectins / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding; D013997:Time Factors; D014312:Trisaccharides / Q000378:metabolism; D014909:Wheat Germ Agglutinins / Q000737:chemistry*
chemical_list: D000485:Allergens; D001672:Biocompatible Materials; D002241:Carbohydrates; D007074:Immunoglobulin G; D037102:Lectins; D037121:Plant Lectins; D011108:Polymers; D014312:Trisaccharides; D014909:Wheat Germ Agglutinins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C041161:chitotriose; D019793:Fluorescein