Multilayer Nanocarrier for the Codelivery of Interferons: A Promising Strategy for Biocompatible and Long-Acting Antiviral Treatment
Thelvia I. Ramos,
Carlos A. Villacis-Aguirre,
Felipe Sandoval Sandoval,
Sarah Martin-Solano,
Viana Manrique-Suárez,
Hortensia Rodríguez,
Leandro Santiago-Padilla,
Alexis Debut,
Carolina Gómez-Gaete,
Marbel Torres Arias,
Raquel Montesino,
Emilio Lamazares,
Ignacio Cabezas,
Florence Hugues,
Natalie C. Parra,
Claudia Altamirano,
Oliberto Sánchez Ramos,
Nelson Santiago-Vispo,
Jorge R. Toledo
Affiliations
Thelvia I. Ramos
Biotechnology and Biopharmaceutical Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción 4030000, Chile
Carlos A. Villacis-Aguirre
Biotechnology and Biopharmaceutical Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción 4030000, Chile
Felipe Sandoval Sandoval
Biotechnology and Biopharmaceutical Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción 4030000, Chile
Sarah Martin-Solano
Grupo de Investigación en Sanidad Animal y Humana (GISAH), Departamento de Ciencias de la Vida y la Agricultura, Universidad de las Fuerzas Armadas ESPE, Sangolquí 171103, Ecuador
Viana Manrique-Suárez
Biotechnology and Biopharmaceutical Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción 4030000, Chile
Hortensia Rodríguez
Yachay Tech Medicinal Chemistry Research Group (MedChem-YT), School of Chemical Science and Engineering, Yachay University for Experimental Technology and Research (Yachay Tech), Yachay City of Knowledge, Urcuqui 100119, Ecuador
Leandro Santiago-Padilla
Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
Alexis Debut
Laboratory of Characterization of Nanomaterials, Center of Nanoscience and Nanotecnology, Universidad de las Fuerzas Armadas ESPE, Sangolquí 171103, Ecuador
Carolina Gómez-Gaete
Department of Pharmacy, Faculty of Pharmacy, Universidad de Concepción, Concepción 4030000, Chile
Marbel Torres Arias
Grupo de Investigación en Sanidad Animal y Humana (GISAH), Departamento de Ciencias de la Vida y la Agricultura, Universidad de las Fuerzas Armadas ESPE, Sangolquí 171103, Ecuador
Raquel Montesino
Biotechnology and Biopharmaceutical Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción 4030000, Chile
Emilio Lamazares
Biotechnology and Biopharmaceutical Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción 4030000, Chile
Ignacio Cabezas
Clinical Sciences Department, Faculty of Veterinary Sciences, Universidad de Concepción, Vicente Méndez 595, Chillán 3780000, Chile
Florence Hugues
Clinical Sciences Department, Faculty of Veterinary Sciences, Universidad de Concepción, Vicente Méndez 595, Chillán 3780000, Chile
Natalie C. Parra
Biotechnology and Biopharmaceutical Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción 4030000, Chile
Claudia Altamirano
Escuela de Ingeniería Bioquímica, Facultad de Ingeniería, Pontificia Universidad Católica de Valparaíso, Av. Brasil 2085, Valparaíso 2362803, Chile
Oliberto Sánchez Ramos
Laboratory of Recombinant Biopharmaceuticals, Departamento de Farmacología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción 4030000, Chile
Biotechnology and Biopharmaceutical Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción 4030000, Chile
Background: Interferons (IFNs) are cytokines involved in the immune response with a synergistic regulatory effect on the immune response. They are therapeutics for various viral and proliferative conditions, with proven safety and efficacy. Their clinical application is challenging due to the molecules’ size, degradation, and pharmacokinetics. We are working on new drug delivery systems that provide adequate therapeutic concentrations for these cytokines and prolong their half-life in the circulation, such as nanoformulations. Methods: Through nanoencapsulation using electrospray technology and biocompatible and biodegradable polymers, we are developing a controlled release system based on nanoparticles for viral infections of the respiratory tract. Results: We developed a controlled release system for viral respiratory tract infections. A prototype nanoparticle with a core was created, which hydrolyzed the polyvinylpyrrolidone (PVP) shell , releasing the active ingredients interferon-alpha (IFN-α) and interferon-gamma (IFN-γ). The chitosan (QS) core degraded slowly, with a controlled release of IFN-α. The primary and rapid effect of the interferon combination ensured an antiviral and immunoregulatory response from day one, induced by IFN-α and enhanced by IFN-γ. The multilayer design demonstrated an optimal toxicity profile. Conclusions: This formulation is an inhaled dry powder intended for the non-invasive intranasal route. The product does not require a cold chain and has the potential for self-administration in the face of emerging viral infections. This novel drug has applications in multiple infectious, oncological, and autoimmune conditions, and further development is proposed for its therapeutic potential. This prototype would ensure greater bioavailability, controlled release, fewer adverse effects, and robust biological action through the simultaneous action of both molecules.