title: Gamma-irradiation effects on biopharmaceutical properties of PLGA microspheres loaded with SPf66 synthetic vaccine.
abstract: Gamma-irradiation is currently the method of choice for terminal sterilization of drug delivery systems made from biodegradable polymers. However, the consequences of gamma-sterilization on the immune response induced by microencapsulated antigens have not yet been reported in the literature. The aim of the present work was to evaluate the effect of gamma-irradiation on the biopharmaceutical properties of PLGA microspheres containing SPf66 malarial antigen. Microspheres were prepared by a (w/o/w) double emulsion/solvent extraction method. Once prepared, part of the formulation was irradiated at a dose of 25 kGy using 60Co gamma as radiation source. The in vitro results obtained showed that the gamma-irradiation exposure had no apparent effect on SPf66 integrity and formulation properties such us morphology, size and peptide loading. Only the release rate of SPf66 was slightly faster after gamma-irradiation. Subcutaneous administration of irradiated and non-irradiated microspheres into mice induced a similar immune response (IgG, IgG1, IgG2a levels) and was comparable to that obtained with SPf66 emulsified with Freund's complete adjuvant. These observations illustrate the applicability of gamma-irradiation as a method of terminal sterilization of microparticulate delivery systems based on chemically synthesized antigens encapsulated into biodegradable PLGA microspheres.
authors.affiliation: University of the Basque Country (UPV-EHU), Vitoria-Gasteiz, Spain.
authors.forename: Manoli
authors.initials: M
authors.lastname: Igartua
authors.forename: Rosa M A
authors.initials: RM
authors.lastname: Hernández
authors.forename: Jaiver Eduardo
authors.initials: JE
authors.lastname: Rosas
authors.forename: Manuel Elkin
authors.initials: ME
authors.lastname: Patarroyo
authors.forename: José Luís
authors.initials: JL
authors.lastname: Pedraz
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000737:chemistry; D001702:Biopharmaceutics; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D004339:Drug Compounding; D005079:Excipients; D005260:Female; D005720:Gamma Rays; D007114:Immunization; D019344:Lactic Acid / Q000737:chemistry* / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000528:radiation effects*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015800:Protozoan Proteins / Q000008:administration & dosage* / Q000737:chemistry; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000737:chemistry; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D001428:Bacterial Vaccines; D005079:Excipients; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C066269:SPf66 protein, Plasmodium; D014614:Vaccines, Synthetic; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid