Polymeric nanoencapsulation of alpha interferon increases drug bioavailability and induces a sustained antiviral response in vivo
Autor: | Seidy Pedroso-Santana, Katherina Fernández, Carolina Gómez-Gaete, Rodrigo Mansilla, Noralvis Fleitas-Salazar, Emilio Lamazares Arcia, A. Ruiz, Jorge Roberto Toledo Alonso, Claudia Altamirano, Marlon Gancino Guevara |
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Rok vydání: | 2020 |
Předmět: |
Materials science
Polymers Swine Alpha interferon Biological Availability Bioengineering 02 engineering and technology Pharmacology 010402 general chemistry 01 natural sciences Antiviral Agents Biomaterials Drug Delivery Systems In vivo Interferon medicine Animals Bovine serum albumin Particle Size Interferon alfa Chitosan Drug Carriers biology Interferon-alpha 021001 nanoscience & nanotechnology 0104 chemical sciences Bioavailability Pharmaceutical Preparations Mechanics of Materials Drug delivery biology.protein Nanoparticles Cattle 0210 nano-technology Drug carrier medicine.drug |
Zdroj: | Materials scienceengineering. C, Materials for biological applications. 116 |
ISSN: | 1873-0191 |
Popis: | 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. |
Databáze: | OpenAIRE |
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