title: Immunogenicity of meningococcal PorA formulations encapsulated in biodegradable microspheres.
abstract: The purpose of our study was to investigate the possibility to microencapsulate liposomes and meningococcal outer membrane vesicles (OMV), both containing neisserial pore protein A (PorA), in biodegradable dextran- and mannan-based microspheres and to study the immunogenicity of the encapsulated PorA formulations. PorA-liposomes and OMV were encapsulated in dextran- or mannan-based microspheres by using an aqueous two-phase system consisting of a polyethylene glycol solution and a methacrylated dextran or mannan solution. The formulations were characterized for size distribution, PorA structure and antigen recovery after release. Calcein-containing model liposomes were used to establish the encapsulation efficiency and release profiles from both types of microspheres. The immunogenicity of the PorA-containing formulations was determined in mice after subcutaneous immunization. Liposomes were encapsulated in dextran and mannan microspheres with a high efficiency (70-90%). Calcein liposomes, after a 5-day lag period, exhibited apparent zero-order release kinetics from both types of microspheres between Days 5 and 10 of incubation in vitro. The total release was 80 and 100% from mannan and dextran microspheres, respectively. The trimeric PorA conformation was preserved in the released liposomes and OMV and the antigen was partly recovered. The immunogenicity of PorA-liposomes and OMV encapsulated in dextran or mannan microspheres was preserved. In conclusion, PorA-liposomes and OMV could be encapsulated in dextran- and mannan-based microspheres with high efficiency. The immunogenicity of encapsulated antigen was preserved.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB, Utrecht, The Netherlands. w.jiskoot@pharm.uu.nl
authors.forename: Carmen
authors.initials: C
authors.lastname: Arigita
authors.forename: Joost
authors.initials: J
authors.lastname: van den Berg
authors.forename: Karin
authors.initials: K
authors.lastname: Wensink
authors.forename: Mies
authors.initials: M
authors.lastname: van Steenbergen
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: Daan J A
authors.initials: DJ
authors.lastname: Crommelin
authors.forename: Gideon F A
authors.initials: GF
authors.lastname: Kersten
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
mesh_terms: D000818:Animals; D001673:Biodegradation, Environmental; D003911:Dextrans / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005079:Excipients / Q000737:chemistry; D020100:Hydrogels; D007074:Immunoglobulin G / Q000097:blood; D008081:Liposomes; D008351:Mannans / Q000737:chemistry; D008689:Methacrylates / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D018272:Porins / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D013997:Time Factors
chemical_list: D003911:Dextrans; D005079:Excipients; D020100:Hydrogels; D007074:Immunoglobulin G; D008081:Liposomes; D008351:Mannans; D008689:Methacrylates; D018272:Porins; C057699:porin protein, Neisseria; C005044:hydroxyethyl methacrylate