Design and influence of γ-irradiation on the biopharmaceutical properties of nanoparticles containing an antigenic complex from Brucella ovis

Despite vaccination campaigns, brucellosis is still one of the most common bacterial zoonosis in the world. This work describes the development of a novel formulation strategy to the delivery of the Brucella ovis antigenic extract (HS) into ovine mucosal surfaces. Thus, HS was entrapped in conventional and mannosylated poly(anhydride) nanoparticles by the solvent displacement method, and the resulting nanosystems were γ-irradiated to accomplish the sterilization required for the ophthalmic administration route. Sterilization, at either 10 kGy or 25 kGy, did not modify the size, morphology and antigen content of the nanoparticles. Similarly, the integrity and antigenicity of the entrapped antigen were not affected by γ-irradiation. The 25 kGy γ-irradiation dose seemed to influence negatively the HS release from the carriers. However, and in accordance with the Pearson's correlation, all the release patterns followed a similar tendency. Furthermore, the stability of the vaccine systems on lachrymal and nasal ovine fluids, showed that γ-irradiation had no significant effects on the vaccine systems. Since all the vaccine systems accomplished the pharmacopoeial biological tests required for γ-irradiation doses under 25 kGy, these results are highly suggestive for the use of HS loaded poly(anhydride) nanoparticles as an efficient vaccine delivery system for brucellosis immunoprophylaxis, especially for ophthalmic administration.