γ-Irradiation effects on biopharmaceutical properties of PLGA microspheres loaded with SPf66 synthetic vaccine

• Published in: European journal of pharmaceutics and biopharmaceutics 2008-06, Vol.69 (2), p.519-526
• Main Authors: Igartua, Manoli, Hernández, Rosa M a, Rosas, Jaiver Eduardo, Patarroyo, Manuel Elkin, Pedraz, José Luís
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - chemistry; Biological and medical sciences; Biopharmaceutics; Calorimetry, Differential Scanning; Chemical Phenomena; Chemistry, Pharmaceutical; Chemistry, Physical; Drug Compounding; Excipients; Female; Gamma Rays; General pharmacology; Immunization; Lactic Acid - chemistry; Lactic Acid - radiation effects; Medical sciences; Mice; Mice, Inbred BALB C; Microscopy, Electron, Scanning; Microspheres; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; PLGA; Polyglycolic Acid - chemistry; Polyglycolic Acid - radiation effects; Protozoan Proteins - administration & dosage; Protozoan Proteins - chemistry; Recombinant Proteins - administration & dosage; Recombinant Proteins - chemistry; SPf66 malarial antigen; Sterilization; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - chemistry; γ-Irradiation
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2007.12.014

γ-Irradiation is currently the method of choice for terminal sterilization of drug delivery systems made from biodegradable polymers. However, the consequences of γ-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 γ-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 γ as radiation source. The in vitro results obtained showed that the γ-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 γ-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 γ-irradiation as a method of terminal sterilization of microparticulate delivery systems based on chemically synthesized antigens encapsulated into biodegradable PLGA microspheres.