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

Autor: Fleitas-Salazar N; Biotecnology and Biopharmaceuticals Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile., Lamazares E; Biotecnology and Biopharmaceuticals Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile., Pedroso-Santana S; Biotecnology and Biopharmaceuticals Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile., Kappes T; Laboratory of Biomaterials, Departamento de Ingeniería Química, Facultad de Ingeniería, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile., Pérez-Alonso A; Departamento de Electrónica e Informática, Universidad Técnica Federico Santa María, Concepción CP. 4030000, Chile., Hidalgo Á; Biotecnology and Biopharmaceuticals Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile., Altamirano C; Laboratorio de Cultivos Celulares, Escuela de Ingeniería Bioquímica, Pontificia Universidad Católica de Valparaíso, 2362803 Valparaíso, Chile., Sánchez O; Recombinant Biopharmaceuticals Laboratory, Departamento de Farmacología, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile., Fernández K; Laboratory of Biomaterials, Departamento de Ingeniería Química, Facultad de Ingeniería, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile., Toledo JR; Biotecnology and Biopharmaceuticals Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile. Electronic address: jotoledo@udec.cl.
Jazyk: angličtina
Zdroj: Biomaterials advances [Biomater Adv] 2022 Dec; Vol. 143, pp. 213167. Date of Electronic Publication: 2022 Oct 21.
DOI: 10.1016/j.bioadv.2022.213167
Abstrakt: 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.
Competing Interests: Conflicts of interest The authors declare no conflict of interest.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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