Polymeric nanoencapsulation of alpha interferon increases drug bioavailability and induces a sustained antiviral response in vivo

Seidy Pedroso-Santana, Emilio Lamazares Arcia, Noralvis Fleitas-Salazar, Marlon Gancino Guevara, Rodrigo Mansilla, Carolina Gómez-Gaete, CLAUDIA VICTORIA ALTAMIRANO GOMEZ, Katherina Fernandez, Alvaro Ruiz, Jorge R. Toledo Alonso

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Article number111260
JournalMaterials Science and Engineering C
Volume116
DOIs
StatePublished - Nov 2020
Externally publishedYes

Keywords

  • Antiviral interferon
  • Drug delivery
  • Ionotropic gelation
  • Nanoparticles
  • Porcine industry

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