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cc-by-nc-nd (c) Adrián Mallén, et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/214480

Development of cationic solid lipid nanoparticles incorporating cholesteryl-9-carboxynonanoate (9CCN) for delivery of antagomiRsto macrophages

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Lipid-based nanoparticles are a useful tool for nucleic acids delivery and have been regarded as a promising approach for diverse diseases. However, off-targets effects are a matter of concern and some strategies to improve selectivity of solid lipid nanoparticles (SLNs) were reported. The goal of this study was to test formulations of SLNs incorporating lipid cholesteryl-9-carboxynonanoate (9CCN) as “eat-me” signal to target antagomiR oligonucleotides to macrophages. We formulate four SLNs, and those with a mean diameter of 200 nm and a Z-potential values between 25 and 40 mV, which allowed the antagomiR binding, were selected for in vitro studies. Cell viability, transfection efficiency and cellular uptake assays were performed within in vitro macrophages using flow cytometry and confocal imaging and the SLNs incorporating 25 mg of 9CCN proved to be the best formulation. Subsequently, we used a labeled antagomiR to study tissue distribution in in-vivo ApoE-/- model of atherosclerosis. Using the ApoE-/- model we demonstrated that SLNs with phagocytic signal 9-CCN target macrophages and release the antagomiR cargo in a selective way.

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MALLÉN, Adrián, NARVÁEZ NARVÁEZ, David a., PUJOL DILMÉ, M. dolors, NAVARRO, Estanis, SUÑÉ I NEGRE, Josep m. (josep maria), GARCÍA MONTOYA, Encarna, PÉREZ LOZANO, Pilar, TORREJÓN-ESCRIBANO, Benjamín, SUÑÉ POU, Marc, HUESO VAL, Miguel. Development of cationic solid lipid nanoparticles incorporating cholesteryl-9-carboxynonanoate (9CCN) for delivery of antagomiRsto macrophages. _European Journal of Pharmaceutics and Biopharmaceutics_. 2024. Vol. 197. [consulta: 1 de gener de 2026]. ISSN: 0939-6411. [Disponible a: https://hdl.handle.net/2445/214480]

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