title: Inactive Vibrio cholerae whole-cell vaccine-loaded biodegradable microparticles: in vitro release and oral vaccination.
abstract: An approach is proposed using Vibrio cholerae (VC)-loaded microparticles as oral vaccine delivery systems for improved vaccine bioavailability and increased therapeutic efficacy. The VC-loaded microparticles were prepared with 50:50 poly(DL-lactide-co-glycolide) (PLG), 75:25 poly(DL-lactide-co-glycolide) and poly(lactide acid) (PLA)/PEG blend copolymers by the solvent evaporation method. VC was successfully entrapped in three types of microparticles with loading efficiencies and loading levels as follows: 50:50 PLG systems: 97.8% and 55.4 +/- 6.9 micro g/mg; 75:25 PLG systems: 89.2% and 46.5 +/- 4.4 micro g/mg; PLA/PEG-blended systems: 82.6% and 53.7 +/- 5.8 micro g/mg. The different distributions of VC in the core region and on the surface were as follows: 50:50 PLG systems 25.7 +/- 1.9 and 6.2 +/- 0.9 micro g/mg; 75:25 PLG systems: 25.8 +/- 2.2 and 3.6 +/- 0.4 micro g/mg; PLA/PEG-blended systems: 32.4 +/- 2.1 and 5.2 +/- 1.0 micro g/mg, respectively. In vitro active release of VC was affected mainly by matrix type and VC-loaded location in microparticles. The therapeutic immunogenic potential of VC loaded with 50:50 PLG, 75:25 PLG and PLA/PEG-blended microparticles was evaluated in adult mice by oral immunization. Significantly higher antibody responses and serum immunoglobin Ig G, IgA and IgM responses were obtained when sera from both VC-loaded 75:25 PLG and PLA/PEG-blended microparticles immunized mice were titrated against VC. The most immunogenicity in evoking serum IgG, IgA and IgM responses was immunized by VC-loaded PLA/PEG-blended microparticles, and with VC challenge in mice, the survival rate (91.7%).
authors.affiliation: Department of Clinical Pharmacy, and Pediatric Tri-service General Hospital, National Defense Medical Center 325, Sec 2 Chen-kung R.D Neihu Taipei (114) Taiwan. mkyeh@ndmctsgh.edu.tw
authors.forename: M- K
authors.initials: M
authors.lastname: Yeh
authors.forename: C- H
authors.initials: C
authors.lastname: Chiang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D002771:Cholera / Q000517:prevention & control*; D022121:Cholera Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D006016:Glycolates / Q000737:chemistry; D019344:Lactic Acid; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014611:Vaccination / Q000379:methods; D015164:Vaccines, Inactivated / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D014734:Vibrio cholerae / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D022121:Cholera Vaccines; D006016:Glycolates; D015164:Vaccines, Inactivated; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid