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Synthesis and Characterization of Mannosylated Formulations to Deliver a Minicircle DNA Vaccine

DNA vaccines still represent an emergent area of research, giving rise to continuous progress towards several biomedicine demands. The formulation of delivery systems to specifically target mannose receptors, which are overexpressed on antigen presenting cells (APCs), is considered a suitable strate...

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Autores principales: Serra, Ana Sofia, Eusébio, Dalinda, Neves, Ana Raquel, Albuquerque, Tânia, Bhatt, Himanshu, Biswas, Swati, Costa, Diana, Sousa, Ângela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150592/
https://www.ncbi.nlm.nih.gov/pubmed/34067176
http://dx.doi.org/10.3390/pharmaceutics13050673
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author Serra, Ana Sofia
Eusébio, Dalinda
Neves, Ana Raquel
Albuquerque, Tânia
Bhatt, Himanshu
Biswas, Swati
Costa, Diana
Sousa, Ângela
author_facet Serra, Ana Sofia
Eusébio, Dalinda
Neves, Ana Raquel
Albuquerque, Tânia
Bhatt, Himanshu
Biswas, Swati
Costa, Diana
Sousa, Ângela
author_sort Serra, Ana Sofia
collection PubMed
description DNA vaccines still represent an emergent area of research, giving rise to continuous progress towards several biomedicine demands. The formulation of delivery systems to specifically target mannose receptors, which are overexpressed on antigen presenting cells (APCs), is considered a suitable strategy to improve the DNA vaccine immunogenicity. The present study developed binary and ternary carriers, based on polyethylenimine (PEI), octa-arginine peptide (R8), and mannose ligands, to specifically deliver a minicircle DNA (mcDNA) vaccine to APCs. Systems were prepared at various nitrogen to phosphate group (N/P) ratios and characterized in terms of their morphology, size, surface charge, and complexation capacity. In vitro studies were conducted to assess the biocompatibility, cell internalization ability, and gene expression of formulated carriers. The high charge density and condensing capacity of both PEI and R8 enhance the interaction with the mcDNA, leading to the formation of smaller particles. The addition of PEI polymer to the R8-mannose/mcDNA binary system reduces the size and increases the zeta potential and system stability. Confocal microscopy studies confirmed intracellular localization of targeting systems, resulting in sustained mcDNA uptake. Furthermore, the efficiency of in vitro transfection can be influenced by the presence of R8-mannose, with great implications for gene expression. R8-mannose/PEI/mcDNA ternary systems can be considered valuable tools to instigate further research, aiming for advances in the DNA vaccine field.
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spelling pubmed-81505922021-05-27 Synthesis and Characterization of Mannosylated Formulations to Deliver a Minicircle DNA Vaccine Serra, Ana Sofia Eusébio, Dalinda Neves, Ana Raquel Albuquerque, Tânia Bhatt, Himanshu Biswas, Swati Costa, Diana Sousa, Ângela Pharmaceutics Article DNA vaccines still represent an emergent area of research, giving rise to continuous progress towards several biomedicine demands. The formulation of delivery systems to specifically target mannose receptors, which are overexpressed on antigen presenting cells (APCs), is considered a suitable strategy to improve the DNA vaccine immunogenicity. The present study developed binary and ternary carriers, based on polyethylenimine (PEI), octa-arginine peptide (R8), and mannose ligands, to specifically deliver a minicircle DNA (mcDNA) vaccine to APCs. Systems were prepared at various nitrogen to phosphate group (N/P) ratios and characterized in terms of their morphology, size, surface charge, and complexation capacity. In vitro studies were conducted to assess the biocompatibility, cell internalization ability, and gene expression of formulated carriers. The high charge density and condensing capacity of both PEI and R8 enhance the interaction with the mcDNA, leading to the formation of smaller particles. The addition of PEI polymer to the R8-mannose/mcDNA binary system reduces the size and increases the zeta potential and system stability. Confocal microscopy studies confirmed intracellular localization of targeting systems, resulting in sustained mcDNA uptake. Furthermore, the efficiency of in vitro transfection can be influenced by the presence of R8-mannose, with great implications for gene expression. R8-mannose/PEI/mcDNA ternary systems can be considered valuable tools to instigate further research, aiming for advances in the DNA vaccine field. MDPI 2021-05-07 /pmc/articles/PMC8150592/ /pubmed/34067176 http://dx.doi.org/10.3390/pharmaceutics13050673 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Serra, Ana Sofia
Eusébio, Dalinda
Neves, Ana Raquel
Albuquerque, Tânia
Bhatt, Himanshu
Biswas, Swati
Costa, Diana
Sousa, Ângela
Synthesis and Characterization of Mannosylated Formulations to Deliver a Minicircle DNA Vaccine
title Synthesis and Characterization of Mannosylated Formulations to Deliver a Minicircle DNA Vaccine
title_full Synthesis and Characterization of Mannosylated Formulations to Deliver a Minicircle DNA Vaccine
title_fullStr Synthesis and Characterization of Mannosylated Formulations to Deliver a Minicircle DNA Vaccine
title_full_unstemmed Synthesis and Characterization of Mannosylated Formulations to Deliver a Minicircle DNA Vaccine
title_short Synthesis and Characterization of Mannosylated Formulations to Deliver a Minicircle DNA Vaccine
title_sort synthesis and characterization of mannosylated formulations to deliver a minicircle dna vaccine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150592/
https://www.ncbi.nlm.nih.gov/pubmed/34067176
http://dx.doi.org/10.3390/pharmaceutics13050673
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