Polyester microparticles as a vaccine delivery system for brucellosis: influence of the polymer on release, phagocytosis and toxicity.
Microparticles, containing an antigenic complex from Brucella ovis (HS), were evaluated for vaccine purposes against brucellosis. They were prepared by the double emulsion solvent evaporation method using two different polyesters, poly-lactide-co-glycolide acid (75:25; RG 756) and poly-epsilon-caprolactone. The encapsulation efficiency and release of HS from the microparticles, their capacity to be phagocytosed and also their toxicity on murine monocytes J774.2 were investigated. Both polymers lead to smooth and spherical sub-5 microm particles, with approximately 30% of the antigen initial dose encapsulated. SDS-PAGE and immunoblot of extracted antigens confirmed that the apparent molecular weight and antigenicity remained unaltered after the encapsulation procedure. However, the in vitro release of the antigens differed among them. The release profile for PLGA microparticles was continuous, whereas PEC ones released the antigens in a triphasic release pattern. Phagocytosis was clearly influenced by the hydrophobicity of the polymer, increasing in the case of PEC microparticles. Toxicity assay showed that both types of microparticles induced similar levels of mitochondrial damage. In conclusion, HS-PEC microparticles could be used as an effective vaccine against brucellosis, as the antigen is released in boosters and they are greatly phagocytosed by macrophages.
Murillo
M
M
Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Navarra, Pamplona, Spain.
Gamazo
C
C
Irache
J M
JM
Goñi
M M
MM
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism; D002002:Brucella / Q000187:drug effects / Q000276:immunology; D002004:Brucella Vaccine / Q000008:administration & dosage*; D002006:Brucellosis / Q000517:prevention & control*; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D019344:Lactic Acid / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects; D011091:Polyesters / Q000008:administration & dosage* / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000494:pharmacology; D014611:Vaccination / Q000379:methods
D000942:Antigens, Bacterial; D002004:Brucella Vaccine; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C062968:lactide-caprolactone copolymer