mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation
The anti-inflammatory cytokine Interleukin-10 (IL-10) is considered an efficient treatment for corneal inflammation, in spite of its short half-life and poor eye bioavailability. In the present work, mRNA-based nanomedicinal products based on solid lipid nanoparticles (SLNs) were developed in order...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/9/1472 |
| _version_ | 1797517544510193664 |
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| author | Itziar Gómez-Aguado Julen Rodríguez-Castejón Marina Beraza-Millor Mónica Vicente-Pascual Alicia Rodríguez-Gascón Sara Garelli Luigi Battaglia Ana del Pozo-Rodríguez María Ángeles Solinís |
| author_facet | Itziar Gómez-Aguado Julen Rodríguez-Castejón Marina Beraza-Millor Mónica Vicente-Pascual Alicia Rodríguez-Gascón Sara Garelli Luigi Battaglia Ana del Pozo-Rodríguez María Ángeles Solinís |
| author_sort | Itziar Gómez-Aguado |
| collection | DOAJ |
| description | The anti-inflammatory cytokine Interleukin-10 (IL-10) is considered an efficient treatment for corneal inflammation, in spite of its short half-life and poor eye bioavailability. In the present work, mRNA-based nanomedicinal products based on solid lipid nanoparticles (SLNs) were developed in order to produce IL-10 to treat corneal inflammation. mRNA encoding green fluorescent protein (GFP) or human IL-10 was complexed with different SLNs and ligands. After, physicochemical characterization, transfection efficacy, intracellular disposition, cellular uptake and IL-10 expression of the nanosystems were evaluated <i>in vitro</i> in human corneal epithelial (HCE-2) cells. Energy-dependent mechanisms favoured HCE-2 transfection, whereas protein production was influenced by energy-independent uptake mechanisms. Nanovectors with a mean particle size between 94 and 348 nm and a positive superficial charge were formulated as eye drops containing 1% (<i>w</i>/<i>v</i>) of polyvinyl alcohol (PVA) with 7.1–7.5 pH. After three days of topical administration to mice, all formulations produced GFP in the corneal epithelium of mice. SLNs allowed the obtaining of a higher transfection efficiency than naked mRNA. All formulations produce IL-10, and the interleukin was even observed in the deeper layers of the epithelium of mice depending on the formulation. This work shows the potential application of mRNA-SLN-based nanosystems to address corneal inflammation by gene augmentation therapy. |
| first_indexed | 2024-03-10T07:18:01Z |
| format | Article |
| id | doaj.art-161894298f584dfe9faeaeb70999b60c |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T07:18:01Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-161894298f584dfe9faeaeb70999b60c2023-11-22T14:48:16ZengMDPI AGPharmaceutics1999-49232021-09-01139147210.3390/pharmaceutics13091472mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 SupplementationItziar Gómez-Aguado0Julen Rodríguez-Castejón1Marina Beraza-Millor2Mónica Vicente-Pascual3Alicia Rodríguez-Gascón4Sara Garelli5Luigi Battaglia6Ana del Pozo-Rodríguez7María Ángeles Solinís8Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, SpainPharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, SpainPharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, SpainPharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, SpainPharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, SpainDipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Pietro Giuria 9, 10125 Torino, ItalyDipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Pietro Giuria 9, 10125 Torino, ItalyPharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, SpainPharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, SpainThe anti-inflammatory cytokine Interleukin-10 (IL-10) is considered an efficient treatment for corneal inflammation, in spite of its short half-life and poor eye bioavailability. In the present work, mRNA-based nanomedicinal products based on solid lipid nanoparticles (SLNs) were developed in order to produce IL-10 to treat corneal inflammation. mRNA encoding green fluorescent protein (GFP) or human IL-10 was complexed with different SLNs and ligands. After, physicochemical characterization, transfection efficacy, intracellular disposition, cellular uptake and IL-10 expression of the nanosystems were evaluated <i>in vitro</i> in human corneal epithelial (HCE-2) cells. Energy-dependent mechanisms favoured HCE-2 transfection, whereas protein production was influenced by energy-independent uptake mechanisms. Nanovectors with a mean particle size between 94 and 348 nm and a positive superficial charge were formulated as eye drops containing 1% (<i>w</i>/<i>v</i>) of polyvinyl alcohol (PVA) with 7.1–7.5 pH. After three days of topical administration to mice, all formulations produced GFP in the corneal epithelium of mice. SLNs allowed the obtaining of a higher transfection efficiency than naked mRNA. All formulations produce IL-10, and the interleukin was even observed in the deeper layers of the epithelium of mice depending on the formulation. This work shows the potential application of mRNA-SLN-based nanosystems to address corneal inflammation by gene augmentation therapy.https://www.mdpi.com/1999-4923/13/9/1472messenger RNAsolid lipid nanoparticlesinterleukin-10corneal inflammationpolyvinyl alcoholtopical administration |
| spellingShingle | Itziar Gómez-Aguado Julen Rodríguez-Castejón Marina Beraza-Millor Mónica Vicente-Pascual Alicia Rodríguez-Gascón Sara Garelli Luigi Battaglia Ana del Pozo-Rodríguez María Ángeles Solinís mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation Pharmaceutics messenger RNA solid lipid nanoparticles interleukin-10 corneal inflammation polyvinyl alcohol topical administration |
| title | mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation |
| title_full | mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation |
| title_fullStr | mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation |
| title_full_unstemmed | mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation |
| title_short | mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation |
| title_sort | mrna based nanomedicinal products to address corneal inflammation by interleukin 10 supplementation |
| topic | messenger RNA solid lipid nanoparticles interleukin-10 corneal inflammation polyvinyl alcohol topical administration |
| url | https://www.mdpi.com/1999-4923/13/9/1472 |
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