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Cholesteryl Oleate-Loaded Cationic Solid Lipid Nanoparticles as Carriers for Efficient Gene-Silencing Therapy

Cholesteryl Oleate-Loaded Cationic Solid Lipid Nanoparticles as Carriers for Efficient Gene-Silencing Therapy

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

Int J Nanomedicine. 2018 May 30;13:3223-3233.

PMID: 29881274

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP303435	Cholesteryl oleate		303-43-5	Price

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