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Polymeric nanoencapsulation of alpha interferon increases drug bioavailability and induces a sustained antiviral response in vivo.
Pedroso-Santana, Seidy; Lamazares Arcia, Emilio; Fleitas-Salazar, Noralvis; Gancino Guevara, Marlon; Mansilla, Rodrigo; Gómez-Gaete, Carolina; Altamirano, Claudia; Fernandez, Katherina; Ruiz, Alvaro; Toledo Alonso, Jorge R.
  • Pedroso-Santana S; Laboratorio de Biotecnología y Biofármacos, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile.
  • Lamazares Arcia E; Laboratorio de Biotecnología y Biofármacos, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile; Centro de Biotecnología y Biomedicina SpA, Granada 168, Vilumanque, Concepción, Chile.
  • Fleitas-Salazar N; Laboratorio de Biotecnología y Biofármacos, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile; Centro de Biotecnología y Biomedicina SpA, Granada 168, Vilumanque, Concepción, Chile.
  • Gancino Guevara M; Laboratorio de Biotecnología y Biofármacos, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile.
  • Mansilla R; Laboratorio de Biotecnología y Biofármacos, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile; Centro de Biotecnología y Biomedicina SpA, Granada 168, Vilumanque, Concepción, Chile.
  • Gómez-Gaete C; Departamento de Farmacia, Facultad de Farmacia, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile; Unidad de Desarrollo Tecnológico UDT, Universidad de Concepción, Chile.
  • Altamirano C; Biochemical Engineering School, Pontificia Universidad Católica de Valparaíso, Av. Brasil 2950, CP. 2390302, Chile.
  • Fernandez K; Laboratory of Biomaterials, Departamento de Ingeniería Química, Facultad de Ingeniería, University of Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile.
  • Ruiz A; Pathology and Preventive Medicine Department, School of Veterinary Sciences, Universidad de Concepción, Av. Vicente Méndez 595, Chillan CP. 3780000, Chile.
  • Toledo Alonso JR; Laboratorio de Biotecnología y Biofármacos, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario s/n, Concepción CP. 4030000, Chile; Centro de Biotecnología y Biomedicina SpA, Granada 168, Vilumanque, Concepción, Chile. Electronic address:
Mater Sci Eng C Mater Biol Appl ; 116: 111260, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1452344
Semantic information from SemMedBD (by NLM)
1. Interferon-alpha CAUSES Antiviral Response
Subject
Interferon-alpha
Predicate
CAUSES
Object
Antiviral Response
2. Recombinant Interferon Alfa PART_OF Family suidae
Subject
Recombinant Interferon Alfa
Predicate
PART_OF
Object
Family suidae
3. Cell Count USES fluorescein
Subject
Cell Count
Predicate
USES
Object
fluorescein
4. Interferon-alpha PART_OF Family suidae
Subject
Interferon-alpha
Predicate
PART_OF
Object
Family suidae
5. Cytotoxicity assay DIAGNOSES Protection
Subject
Cytotoxicity assay
Predicate
DIAGNOSES
Object
Protection
6. Cell Count DIAGNOSES Present
Subject
Cell Count
Predicate
DIAGNOSES
Object
Present
7. Interferon-alpha CAUSES Antiviral Response
Subject
Interferon-alpha
Predicate
CAUSES
Object
Antiviral Response
8. Recombinant Interferon Alfa PART_OF Family suidae
Subject
Recombinant Interferon Alfa
Predicate
PART_OF
Object
Family suidae
9. Cell Count USES fluorescein
Subject
Cell Count
Predicate
USES
Object
fluorescein
10. Interferon-alpha PART_OF Family suidae
Subject
Interferon-alpha
Predicate
PART_OF
Object
Family suidae
11. Cytotoxicity assay DIAGNOSES Protection
Subject
Cytotoxicity assay
Predicate
DIAGNOSES
Object
Protection
12. Cell Count DIAGNOSES Present
Subject
Cell Count
Predicate
DIAGNOSES
Object
Present
ABSTRACT
Polymeric nanoparticulate systems allow the encapsulation of bio-active substances, giving them protection against external agents and increasing the drug's bioavailability. The use of biocompatible and biodegradable polymers usually guarantees the harmless character of the formulation, and a controlled drug release is also assured. A relatively easy procedure to obtain polymeric formulations of bioactive agents is ionotropic gelation, which allows the synthesis of chitosan (CS) - sodium tri-polyphosphate nanoparticles (NPs) loading encapsulated proteins. In this work, Bovine serum albumin (BSA) model protein and a recombinant porcine alpha interferon variant were used to obtain nanoparticulate formulations. The internalization of the encapsulated material by cells was studied using a BSA-fluorescein system; the fluorescent conjugate was observable inside the cells after 20 h of incubation. The therapeutic CS-alpha interferon formulation showed a maximum of protein released in vitro at around 90 h. This system was found to be safe in a cytotoxicity assay, while biological activity experiments in vitro showed antiviral protection of cells in the presence of encapsulated porcine alpha interferon. In vivo experiments in pigs revealed a significant and sustained antiviral response through overexpression of the antiviral markers OAS2 and PKR. This proves the preservation of porcine alpha interferon biological activity, and also that a lasting response was obtained. This procedure is an effective and safe method to formulate drugs in nanoparticulate systems, representing a significant contribution to the search for more effective drug delivery strategies.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Pharmaceutical Preparations / Chitosan / Nanoparticles Subject: Pharmaceutical Preparations / Chitosan / Nanoparticles Language: English Journal: Mater Sci Eng C Mater Biol Appl Year: 2020

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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Pharmaceutical Preparations / Chitosan / Nanoparticles Subject: Pharmaceutical Preparations / Chitosan / Nanoparticles Language: English Journal: Mater Sci Eng C Mater Biol Appl Year: 2020
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