Abstract

Effective cytokine treatments often require high-and multiple-dose due to the short half-life of these molecules. Here, porcine interferon-alpha (IFN alpha) is encapsulated in PLGA-chitosan microparticles (IFN alpha-MPs) to accomplish both slow drug release and drug protection from degradation. A procedure that combines emulsion and spray -drying techniques yielded almost spherical microspheres with an average diameter of 3.00 +/- 1.50 mu m. SEM, Microtrac, and Z-potential analyses of three IFN alpha-MP batches showed similar results, indicating the process is reproducible. These studies supported molecular evidence obtained in FTIR analysis, which indicated a compact structure of IFN alpha-MPs. Consistently, IFN alpha release kinetics assessed in vitro followed a zero-order behavior typical of sustained release from a polymeric matrix. This study showed that IFN alpha-MPs released bioactive molecules for at least 15 days, achieving IFN alpha protection. In addition, pigs treated with IFN alpha-MPs exhibited overexpression of IFN alpha-stimulated genes 16 days after treatment. Instead, the expression levels of these genes decreased after day 4th in pigs treated with non-encapsulated IFN alpha. In vitro and in vivo experiments demonstrated that the formu-lation improved the prophylactic and therapeutic potential of IFN alpha, accomplishing molecule protection and long-term release for at least two weeks. The procedure used to obtain IFN alpha-MPs is reproducible, scalable, and suitable for encapsulating other drugs.