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MRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation.

ABSTRACT: 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 in vitro 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% (w/v) 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.

SUBMITTER: Gomez-Aguado I

PROVIDER: S-EPMC8466377 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation.

Gómez-Aguado Itziar I Rodríguez-Castejón Julen J Beraza-Millor Marina M Vicente-Pascual Mónica M Rodríguez-Gascón Alicia A Garelli Sara S Battaglia Luigi L Del Pozo-Rodríguez Ana A Solinís María Ángeles MÁ

Pharmaceutics 20210915 9

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, tra ...[more]

PMID: 34575548

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Dataset Information

MRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation.

Publications

mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation.

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