Evaluation of Poly(<i>N</i>-Ethyl Pyrrolidine Methacrylamide) (EPA) and Derivatives as Polymeric Vehicles for miRNA Delivery to Neural Cells
MicroRNAs (miRNAs) are endogenous, short RNA oligonucleotides that regulate the expression of hundreds of proteins to control cells’ function in physiological and pathological conditions. miRNA therapeutics are highly specific, reducing the toxicity associated with off-target effects, and require lo...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/5/1451 |
| _version_ | 1797598675250184192 |
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| author | Altea Soto Manuel Nieto-Díaz Enrique Martínez-Campos Ana Noalles-Dols María Asunción Barreda-Manso Felipe Reviriego Helmut Reinecke David Reigada Teresa Muñoz-Galdeano Irene Novillo Alberto Gallardo Juan Rodríguez-Hernández Ramón Eritja Anna Aviñó Carlos Elvira Rodrigo M. Maza |
| author_facet | Altea Soto Manuel Nieto-Díaz Enrique Martínez-Campos Ana Noalles-Dols María Asunción Barreda-Manso Felipe Reviriego Helmut Reinecke David Reigada Teresa Muñoz-Galdeano Irene Novillo Alberto Gallardo Juan Rodríguez-Hernández Ramón Eritja Anna Aviñó Carlos Elvira Rodrigo M. Maza |
| author_sort | Altea Soto |
| collection | DOAJ |
| description | MicroRNAs (miRNAs) are endogenous, short RNA oligonucleotides that regulate the expression of hundreds of proteins to control cells’ function in physiological and pathological conditions. miRNA therapeutics are highly specific, reducing the toxicity associated with off-target effects, and require low doses to achieve therapeutic effects. Despite their potential, applying miRNA-based therapies is limited by difficulties in delivery due to their poor stability, fast clearance, poor efficiency, and off-target effects. To overcome these challenges, polymeric vehicles have attracted a lot of attention due to their ease of production with low costs, large payload, safety profiles, and minimal induction of the immune response. Poly(<i>N</i>-ethyl pyrrolidine methacrylamide) (EPA) copolymers have shown optimal DNA transfection efficiencies in fibroblasts. The present study aims to evaluate the potential of EPA polymers as miRNA carriers for neural cell lines and primary neuron cultures when they are copolymerized with different compounds. To achieve this aim, we synthesized and characterized different copolymers and evaluated their miRNA condensation ability, size, charge, cytotoxicity, cell binding and internalization ability, and endosomal escape capacity. Finally, we evaluated their miRNA transfection capability and efficacy in Neuro-2a cells and rat primary hippocampal neurons. The results indicate that EPA and its copolymers, incorporating β-cyclodextrins with or without polyethylene glycol acrylate derivatives, can be promising vehicles for miRNA administration to neural cells when all experiments on Neuro-2a cells and primary hippocampal neurons are considered together. |
| first_indexed | 2024-03-11T03:24:25Z |
| format | Article |
| id | doaj.art-6e336ec2b6154f558aa9aad96f96bacf |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T03:24:25Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-6e336ec2b6154f558aa9aad96f96bacf2023-11-18T02:51:54ZengMDPI AGPharmaceutics1999-49232023-05-01155145110.3390/pharmaceutics15051451Evaluation of Poly(<i>N</i>-Ethyl Pyrrolidine Methacrylamide) (EPA) and Derivatives as Polymeric Vehicles for miRNA Delivery to Neural CellsAltea Soto0Manuel Nieto-Díaz1Enrique Martínez-Campos2Ana Noalles-Dols3María Asunción Barreda-Manso4Felipe Reviriego5Helmut Reinecke6David Reigada7Teresa Muñoz-Galdeano8Irene Novillo9Alberto Gallardo10Juan Rodríguez-Hernández11Ramón Eritja12Anna Aviñó13Carlos Elvira14Rodrigo M. Maza15Molecular Neuroprotection Group, Hospital Nacional de Parapléjicos (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Hospital Nacional de Parapléjicos (SESCAM), 45071 Toledo, SpainPolymer Functionalization Group, Instituto de Ciencia y Tecnología de Polímeros-Consejo Superior de Investigaciones Científicas (ICTP-CSIC), Departamento de Química Macromolecular Aplicada, Juan de la Cierva 3, 28006 Madrid, SpainMolecular Neuroprotection Group, Hospital Nacional de Parapléjicos (SESCAM), 45071 Toledo, SpainFunctional Exploration and Neuromodulation of the Central Nervous System Group, Hospital Nacional de Parapléjicos (SESCAM), 45071 Toledo, SpainPolymer Functionalization Group, Instituto de Ciencia y Tecnología de Polímeros-Consejo Superior de Investigaciones Científicas (ICTP-CSIC), Departamento de Química Macromolecular Aplicada, Juan de la Cierva 3, 28006 Madrid, SpainPolymer Functionalization Group, Instituto de Ciencia y Tecnología de Polímeros-Consejo Superior de Investigaciones Científicas (ICTP-CSIC), Departamento de Química Macromolecular Aplicada, Juan de la Cierva 3, 28006 Madrid, SpainMolecular Neuroprotection Group, Hospital Nacional de Parapléjicos (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Hospital Nacional de Parapléjicos (SESCAM), 45071 Toledo, SpainMolecular Neuroprotection Group, Hospital Nacional de Parapléjicos (SESCAM), 45071 Toledo, SpainPolymer Functionalization Group, Instituto de Ciencia y Tecnología de Polímeros-Consejo Superior de Investigaciones Científicas (ICTP-CSIC), Departamento de Química Macromolecular Aplicada, Juan de la Cierva 3, 28006 Madrid, SpainPolymer Functionalization Group, Instituto de Ciencia y Tecnología de Polímeros-Consejo Superior de Investigaciones Científicas (ICTP-CSIC), Departamento de Química Macromolecular Aplicada, Juan de la Cierva 3, 28006 Madrid, SpainDepartment of Surfactants and Nanobiotechnology, Institute for Advanced Chemistry of Catalonia (IQAC), Spanish National Research Council (CSIC), Jordi Girona 18-26, 08034 Barcelona, SpainDepartment of Surfactants and Nanobiotechnology, Institute for Advanced Chemistry of Catalonia (IQAC), Spanish National Research Council (CSIC), Jordi Girona 18-26, 08034 Barcelona, SpainPolymer Functionalization Group, Instituto de Ciencia y Tecnología de Polímeros-Consejo Superior de Investigaciones Científicas (ICTP-CSIC), Departamento de Química Macromolecular Aplicada, Juan de la Cierva 3, 28006 Madrid, SpainMolecular Neuroprotection Group, Hospital Nacional de Parapléjicos (SESCAM), 45071 Toledo, SpainMicroRNAs (miRNAs) are endogenous, short RNA oligonucleotides that regulate the expression of hundreds of proteins to control cells’ function in physiological and pathological conditions. miRNA therapeutics are highly specific, reducing the toxicity associated with off-target effects, and require low doses to achieve therapeutic effects. Despite their potential, applying miRNA-based therapies is limited by difficulties in delivery due to their poor stability, fast clearance, poor efficiency, and off-target effects. To overcome these challenges, polymeric vehicles have attracted a lot of attention due to their ease of production with low costs, large payload, safety profiles, and minimal induction of the immune response. Poly(<i>N</i>-ethyl pyrrolidine methacrylamide) (EPA) copolymers have shown optimal DNA transfection efficiencies in fibroblasts. The present study aims to evaluate the potential of EPA polymers as miRNA carriers for neural cell lines and primary neuron cultures when they are copolymerized with different compounds. To achieve this aim, we synthesized and characterized different copolymers and evaluated their miRNA condensation ability, size, charge, cytotoxicity, cell binding and internalization ability, and endosomal escape capacity. Finally, we evaluated their miRNA transfection capability and efficacy in Neuro-2a cells and rat primary hippocampal neurons. The results indicate that EPA and its copolymers, incorporating β-cyclodextrins with or without polyethylene glycol acrylate derivatives, can be promising vehicles for miRNA administration to neural cells when all experiments on Neuro-2a cells and primary hippocampal neurons are considered together.https://www.mdpi.com/1999-4923/15/5/1451poly (<i>N</i>-ethyl pyrrolidine methacrylamide)polymeric delivery systemsmiRNA transfectionneural cellsneuronsin vitro analyses |
| spellingShingle | Altea Soto Manuel Nieto-Díaz Enrique Martínez-Campos Ana Noalles-Dols María Asunción Barreda-Manso Felipe Reviriego Helmut Reinecke David Reigada Teresa Muñoz-Galdeano Irene Novillo Alberto Gallardo Juan Rodríguez-Hernández Ramón Eritja Anna Aviñó Carlos Elvira Rodrigo M. Maza Evaluation of Poly(<i>N</i>-Ethyl Pyrrolidine Methacrylamide) (EPA) and Derivatives as Polymeric Vehicles for miRNA Delivery to Neural Cells Pharmaceutics poly (<i>N</i>-ethyl pyrrolidine methacrylamide) polymeric delivery systems miRNA transfection neural cells neurons in vitro analyses |
| title | Evaluation of Poly(<i>N</i>-Ethyl Pyrrolidine Methacrylamide) (EPA) and Derivatives as Polymeric Vehicles for miRNA Delivery to Neural Cells |
| title_full | Evaluation of Poly(<i>N</i>-Ethyl Pyrrolidine Methacrylamide) (EPA) and Derivatives as Polymeric Vehicles for miRNA Delivery to Neural Cells |
| title_fullStr | Evaluation of Poly(<i>N</i>-Ethyl Pyrrolidine Methacrylamide) (EPA) and Derivatives as Polymeric Vehicles for miRNA Delivery to Neural Cells |
| title_full_unstemmed | Evaluation of Poly(<i>N</i>-Ethyl Pyrrolidine Methacrylamide) (EPA) and Derivatives as Polymeric Vehicles for miRNA Delivery to Neural Cells |
| title_short | Evaluation of Poly(<i>N</i>-Ethyl Pyrrolidine Methacrylamide) (EPA) and Derivatives as Polymeric Vehicles for miRNA Delivery to Neural Cells |
| title_sort | evaluation of poly i n i ethyl pyrrolidine methacrylamide epa and derivatives as polymeric vehicles for mirna delivery to neural cells |
| topic | poly (<i>N</i>-ethyl pyrrolidine methacrylamide) polymeric delivery systems miRNA transfection neural cells neurons in vitro analyses |
| url | https://www.mdpi.com/1999-4923/15/5/1451 |
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