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

• Main Authors: 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
• Format: Article
• Language: English
• Published: MDPI AG 2021-09-01
• Series: Pharmaceutics
• Subjects: messenger RNA; solid lipid nanoparticles; interleukin-10; corneal inflammation; polyvinyl alcohol; topical administration
• Online Access: https://www.mdpi.com/1999-4923/13/9/1472

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.