Immunogenicity of meningococcal PorA formulations encapsulated in biodegradable microspheres.
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.
Arigita
Carmen
C
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
van den Berg
Joost
J
Wensink
Karin
K
van Steenbergen
Mies
M
Hennink
Wim E
WE
Crommelin
Daan J A
DJ
Kersten
Gideon F A
GF
Jiskoot
Wim
W
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
D003911:Dextrans; D005079:Excipients; D020100:Hydrogels; D007074:Immunoglobulin G; D008081:Liposomes; D008351:Mannans; D008689:Methacrylates; D018272:Porins; C057699:porin protein, Neisseria; C005044:hydroxyethyl methacrylate