title: Spray-dried polyelectrolyte microparticles in oral antigen delivery: stability, biocompatibility, and cellular uptake.
abstract: During the past decade, extensive research has undeniably improved the formulation and delivery of oral vaccines. Nevertheless, several factors, such as the harsh gastrointestinal environment together with tolerance induction to exogenous antigens, have thus far impeded the optimal effectiveness and clinical application of oral delivery systems. The current study encompasses an initial evaluation of the stability, biocompatibility, and cellular uptake of two promising candidate systems for oral antigen delivery, that is, calcium carbonate- (CP) and mannitol-templated (MP) porous microspheres. Both spray-dried formulations were efficiently internalized by human intestinal epithelial cells (Caco-2 and HT-29) and degraded into phagolysosomal intracellular compartments. In addition, cellular particle uptake and processing significantly up-regulated the expression of (HLA) class-II and costimulatory molecules on intestinal epithelial cells. Even though the high surface-area-to-volume ratio of the microspheres was expected to favor protease access, antigen release was remarkably limited in simulated intestinal fluid and was even absent under gastric conditions. Finally, neither CP nor MP exerted cytotoxicity upon prolonged in vitro incubation with high antigen concentration. Altogether, these data support the potential of CP and MP for oral antigen delivery and motivate the further development of these promising carrier systems in in vivo studies.
authors.affiliation: Department of Pathology, Ghent University , 5 Blok A, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Rebecca
authors.initials: R
authors.lastname: De Smet
authors.forename: Stephanie
authors.initials: S
authors.lastname: Verschuere
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Allais
authors.forename: Georges
authors.initials: G
authors.lastname: Leclercq
authors.forename: Marijke
authors.initials: M
authors.lastname: Dierendonck
authors.forename: Bruno G
authors.initials: BG
authors.lastname: De Geest
authors.forename: Isabel
authors.initials: I
authors.lastname: Van Driessche
authors.forename: Tine
authors.initials: T
authors.lastname: Demoor
authors.forename: Claude A
authors.initials: CA
authors.lastname: Cuvelier
mesh_terms: D000284:Administration, Oral; D000941:Antigens / Q000008:administration & dosage / Q000378:metabolism*; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000378:metabolism*; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D019073:HT29 Cells; D006801:Humans; D008863:Microspheres; D010047:Ovalbumin / Q000008:administration & dosage / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D000941:Antigens; D001672:Biocompatible Materials; D012710:Serum Albumin, Bovine; D010047:Ovalbumin