Cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy

Marc Suñé-Pou,1–3 Silvia Prieto-Sánchez,2 Younes El Yousfi,2 Sofía Boyero-Corral,2 Anna Nardi-Ricart,1 Isaac Nofrerias-Roig,1 Pilar Pérez-Lozano,1,3 Encarna García-Montoya,1,3 Montserrat Miñarro-Carmona,1,3 Josep...

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Autores principales:	Suñé-Pou M, Prieto-Sánchez S, El Yousfi Y, Boyero-Corral S, Nardi-Ricart A, Nofrerias-Roig I, Pérez-Lozano P, García-Montoya E, Miñarro-Carmona M, Ticó JR, Suñé-Negre JM, Hernández-Munain C, Suñé C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Cationic solid lipid nanoparticles (SLNs) cholesteryl oleate plasmid DNA siRNA transfection Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c7555702cc9a4cfcaa24e0ede19b1c7d
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spelling	oai:doaj.org-article:c7555702cc9a4cfcaa24e0ede19b1c7d2021-12-02T02:20:04ZCholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy1178-2013https://doaj.org/article/c7555702cc9a4cfcaa24e0ede19b1c7d2018-05-01T00:00:00Zhttps://www.dovepress.com/cholesteryl-oleate-loaded-cationic-solid-lipid-nanoparticles-as-carrie-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Marc Suñé-Pou,1–3 Silvia Prieto-Sánchez,2 Younes El Yousfi,2 Sofía Boyero-Corral,2 Anna Nardi-Ricart,1 Isaac Nofrerias-Roig,1 Pilar Pérez-Lozano,1,3 Encarna García-Montoya,1,3 Montserrat Miñarro-Carmona,1,3 Josep Ramón Ticó,1,3 Josep Mª Suñé-Negre,1,3 Cristina Hernández-Munain,4 Carlos Suñé2 1Service of Development of Medicines (SDM), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain; 2Department of Molecular Biology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN-CSIC), Granada, Spain; 3Pharmacotherapy, Pharmacogenetics and Pharmaceutical Technology Research Group, IDIBELL-UB, Duran i Reynals Hospital, Hospitalet de Llobregat, Barcelona, Spain; 4Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN-CSIC), Granada, Spain Background: Cationic solid lipid nanoparticles (SLNs) have been given considerable attention for therapeutic nucleic acid delivery owing to their advantages over viral and other nanoparticle delivery systems. However, poor delivery efficiency and complex formulations hinder the clinical translation of SLNs. Aim: The aim of this study was to formulate and characterize SLNs incorporating the cholesterol derivative cholesteryl oleate to produce SLN–nucleic acid complexes with reduced cytotoxicity and more efficient cellular uptake. Methods: Five cholesteryl oleate-containing formulations were prepared. Laser diffraction and laser Doppler microelectrophoresis were used to evaluate particle size and zeta potential, respectively. Nanoparticle morphology was analyzed using electron microscopy. Cytotoxicity and cellular uptake of lipoplexes were evaluated using flow cytometry and fluorescence microscopy. The gene inhibition capacity of the lipoplexes was assessed using siRNAs to block constitutive luciferase expression. Results: We obtained nanoparticles with a mean diameter of approximately 150–200 nm in size and zeta potential values of 25–40 mV. SLN formulations with intermediate concentrations of cholesteryl oleate exhibited good stability and spherical structures with no aggregation. No cell toxicity of any reference SLN was observed. Finally, cellular uptake experiments with DNA- and RNA-SLNs were performed to select one reference with superior transient transfection efficiency that significantly decreased gene activity upon siRNA complexation. Conclusion: The results indicate that cholesteryl oleate-loaded SLNs are a safe and effective platform for nonviral nucleic acid delivery. Keywords: cationic solid lipid nanoparticles, SLNs, cholesteryl oleate, plasmid DNA, siRNA, transfection, cytotoxicity, uptakeSuñé-Pou MPrieto-Sánchez SEl Yousfi YBoyero-Corral SNardi-Ricart ANofrerias-Roig IPérez-Lozano PGarcía-Montoya EMiñarro-Carmona MTicó JRSuñé-Negre JMHernández-Munain CSuñé CDove Medical PressarticleCationic solid lipid nanoparticles (SLNs)cholesteryl oleateplasmid DNAsiRNAtransfectionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3223-3233 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cationic solid lipid nanoparticles (SLNs) cholesteryl oleate plasmid DNA siRNA transfection Medicine (General) R5-920
spellingShingle	Cationic solid lipid nanoparticles (SLNs) cholesteryl oleate plasmid DNA siRNA transfection Medicine (General) R5-920 Suñé-Pou M Prieto-Sánchez S El Yousfi Y Boyero-Corral S Nardi-Ricart A Nofrerias-Roig I Pérez-Lozano P García-Montoya E Miñarro-Carmona M Ticó JR Suñé-Negre JM Hernández-Munain C Suñé C Cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy
description	Marc Suñé-Pou,1–3 Silvia Prieto-Sánchez,2 Younes El Yousfi,2 Sofía Boyero-Corral,2 Anna Nardi-Ricart,1 Isaac Nofrerias-Roig,1 Pilar Pérez-Lozano,1,3 Encarna García-Montoya,1,3 Montserrat Miñarro-Carmona,1,3 Josep Ramón Ticó,1,3 Josep Mª Suñé-Negre,1,3 Cristina Hernández-Munain,4 Carlos Suñé2 1Service of Development of Medicines (SDM), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain; 2Department of Molecular Biology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN-CSIC), Granada, Spain; 3Pharmacotherapy, Pharmacogenetics and Pharmaceutical Technology Research Group, IDIBELL-UB, Duran i Reynals Hospital, Hospitalet de Llobregat, Barcelona, Spain; 4Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN-CSIC), Granada, Spain Background: Cationic solid lipid nanoparticles (SLNs) have been given considerable attention for therapeutic nucleic acid delivery owing to their advantages over viral and other nanoparticle delivery systems. However, poor delivery efficiency and complex formulations hinder the clinical translation of SLNs. Aim: The aim of this study was to formulate and characterize SLNs incorporating the cholesterol derivative cholesteryl oleate to produce SLN–nucleic acid complexes with reduced cytotoxicity and more efficient cellular uptake. Methods: Five cholesteryl oleate-containing formulations were prepared. Laser diffraction and laser Doppler microelectrophoresis were used to evaluate particle size and zeta potential, respectively. Nanoparticle morphology was analyzed using electron microscopy. Cytotoxicity and cellular uptake of lipoplexes were evaluated using flow cytometry and fluorescence microscopy. The gene inhibition capacity of the lipoplexes was assessed using siRNAs to block constitutive luciferase expression. Results: We obtained nanoparticles with a mean diameter of approximately 150–200 nm in size and zeta potential values of 25–40 mV. SLN formulations with intermediate concentrations of cholesteryl oleate exhibited good stability and spherical structures with no aggregation. No cell toxicity of any reference SLN was observed. Finally, cellular uptake experiments with DNA- and RNA-SLNs were performed to select one reference with superior transient transfection efficiency that significantly decreased gene activity upon siRNA complexation. Conclusion: The results indicate that cholesteryl oleate-loaded SLNs are a safe and effective platform for nonviral nucleic acid delivery. Keywords: cationic solid lipid nanoparticles, SLNs, cholesteryl oleate, plasmid DNA, siRNA, transfection, cytotoxicity, uptake
format	article
author	Suñé-Pou M Prieto-Sánchez S El Yousfi Y Boyero-Corral S Nardi-Ricart A Nofrerias-Roig I Pérez-Lozano P García-Montoya E Miñarro-Carmona M Ticó JR Suñé-Negre JM Hernández-Munain C Suñé C
author_facet	Suñé-Pou M Prieto-Sánchez S El Yousfi Y Boyero-Corral S Nardi-Ricart A Nofrerias-Roig I Pérez-Lozano P García-Montoya E Miñarro-Carmona M Ticó JR Suñé-Negre JM Hernández-Munain C Suñé C
author_sort	Suñé-Pou M
title	Cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy
title_short	Cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy
title_full	Cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy
title_fullStr	Cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy
title_full_unstemmed	Cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy
title_sort	cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/c7555702cc9a4cfcaa24e0ede19b1c7d
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Cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy

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