A new optimized formulation of cationic solid lipid nanoparticles intended for gene delivery: Development, characterization and DNA binding efficiency of TCERG1 expression plasmid

• Published in: International journal of pharmaceutics Vol. 473; no. 1-2; pp. 270 - 279
• Main Authors: Fàbregas, Anna, Sánchez-Hernández, Noemí, Ticó, Josep Ramon, García-Montoya, Encarna, Pérez-Lozano, Pilar, Suñé-Negre, Josep M., Hernández-Munain, Cristina, Suñé, Carlos, Miñarro, Montserrat
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2014
• Subjects: Calorimetry, Differential Scanning; Cationic solid lipid nanoparticles development; Cell Survival - drug effects; Cell viability; Chemistry, Pharmaceutical; DNA - chemistry; DNA binding efficiency; Gene Transfer Techniques; HEK293 Cells; Humans; Lipids - administration & dosage; Lipids - chemistry; Mass Spectrometry; Microscopy, Atomic Force; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Photoelectron Spectroscopy; Plasmid DNA; Plasmids; Solid lipid nanoparticles characterization; Transcriptional Elongation Factors - genetics; X-Ray Diffraction; Cell viability; Plasmid DNA; Solid lipid nanoparticles characterization; Cationic solid lipid nanoparticles development; DNA binding efficiency
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2014.06.022

[Display omitted] Solid lipid nanoparticles (SLNs) are being considered as a new approach for therapeutics for many known diseases. In addition to drug delivery, their use as non-viral vectors for gene delivery can be achieved by the inclusion of cationic lipids, which provide a positive surface potential that favours binding to the DNA backbone. This work is based on the idea that the optimization of the components is required as the first step in simplifying the qualitative and quantitative composition of SLNs as much as possible without affecting the essential properties that define SLNs as optimal non-viral vectors for gene delivery. We selected the best lipids and surfactants in terms of particle size and zeta potential and characterized the properties of the resulting nanoparticles using X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The SLNs had a particle size of approximately 120nm and a positive surface charge of 42mV. In addition, we analysed the main physicochemical characteristics of the bulk components of the nanoparticles using X-ray diffraction (XRD), differential scanning calorimetry (DSC) and mass spectrometry (MS). The suitability of the optimized SLNs for DNA binding was evaluated after the lyophilisation process using a carboxyl-terminal region of the TCERG1 gene, a human factor that has been implicated in several diseases. We show that the SLNs presented high efficiency in the binding of DNA, and importantly, they presented no toxicity when assayed in an in vivo system.