Long-term release of bioactive interferon-alpha from PLGA-chitosan microparticles: in vitro and in vivo studies

Noralvis Fleitas-Salazar, Emilio Lamazares, Seidy Pedroso-Santana, Tomás Kappes, Alain Pérez-Alonso, Ángela Hidalgo, Claudia Altamirano, Oliberto Sánchez, Katherina Fernández, Jorge R. Toledo

Research output: Contribution to journalArticlepeer-review

Abstract

Effective cytokine treatments often require high- and multiple-dose due to the short half-life of these molecules. Here, porcine interferon-alpha (IFNα) is encapsulated in PLGA-chitosan microparticles (IFNα-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 μm. SEM, Microtrac, and Z-potential analyses of three IFNα-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 IFNα-MPs. Consistently, IFNα release kinetics assessed in vitro followed a zero-order behavior typical of sustained release from a polymeric matrix. This study showed that IFNα-MPs released bioactive molecules for at least 15 days, achieving IFNα protection. In addition, pigs treated with IFNα-MPs exhibited overexpression of IFNα-stimulated genes 16 days after treatment. Instead, the expression levels of these genes decreased after day 4th in pigs treated with non-encapsulated IFNα. In vitro and in vivo experiments demonstrated that the formulation improved the prophylactic and therapeutic potential of IFNα, accomplishing molecule protection and long-term release for at least two weeks. The procedure used to obtain IFNα-MPs is reproducible, scalable, and suitable for encapsulating other drugs.

Original languageEnglish
Article number213167
JournalBiomaterials Advances
Volume143
DOIs
StatePublished - Dec 2022
Externally publishedYes

Keywords

  • Chitosan
  • Cytokine
  • Drug delivery
  • FTIR
  • Poly (D, L-lactide-co-glycolide)
  • Polymeric microparticle
  • Porcine interferon alpha
  • Spray-drying

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