2024-03-29T08:35:06Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1839612021-12-27T16:28:18Zcom_10261_64com_10261_1col_10261_317
Suñé-Pou, Marc
Prieto-Sánchez, Silvia
El Yousfi, Younes
Boyero-Corral, Sofía
Nardi-Ricart, Anna
Nofrerias-Roig, Isaac
Pérez-Lozano, Pilar
García-Montoya, Encarna
Minarro-Carmona, Montserrat
Ramón Tico, Josep
Suñé-Negre, Josep Mª
Hernández-Munaín, Cristina
Suñé, Carlos
2019-06-13T10:17:04Z
2019-06-13T10:17:04Z
2018
International Journal of Nanomedicine
1176-9114
http://hdl.handle.net/10261/183961
10.2147/IJN.S158884
1178-2013
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100011011
29881274
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.
eng
openAccess
Cationic solid lipid nanoparticles (SLNs)
SLNs
Cholesteryl oleate
plasmid DNA
siRNA
transfection
Cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy
artículo