title: A new optimized formulation of cationic solid lipid nanoparticles intended for gene delivery: development, characterization and DNA binding efficiency of TCERG1 expression plasmid.
abstract: 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 120 nm and a positive surface charge of 42 mV. 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.
authors.affiliation: Drug Development Service, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Avda. Joan XXIII, s/n 08028 Barcelona, Spain. Electronic address: afabregas@ub.edu.
authors.forename: Anna
authors.initials: A
authors.lastname: Fàbregas
authors.affiliation: Department of Molecular Biology, Instituto de Parasitología y Biomedicina "López-Neyra", Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), 18016 Granada, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Sánchez-Hernández
authors.affiliation: Drug Development Service, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Avda. Joan XXIII, s/n 08028 Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Spain.
authors.forename: Josep Ramon
authors.initials: JR
authors.lastname: Ticó
authors.affiliation: Drug Development Service, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Avda. Joan XXIII, s/n 08028 Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Spain.
authors.forename: Encarna
authors.initials: E
authors.lastname: García-Montoya
authors.affiliation: Drug Development Service, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Avda. Joan XXIII, s/n 08028 Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Pérez-Lozano
authors.affiliation: Drug Development Service, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Avda. Joan XXIII, s/n 08028 Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Suñé-Negre
authors.affiliation: Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López-Neyra", Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), 18016 Granada, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández-Munain
authors.affiliation: Department of Molecular Biology, Instituto de Parasitología y Biomedicina "López-Neyra", Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), 18016 Granada, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Suñé
authors.affiliation: Drug Development Service, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Avda. Joan XXIII, s/n 08028 Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Miñarro
mesh_terms: D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004247:DNA / Q000737:chemistry*; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry; D013058:Mass Spectrometry; D018625:Microscopy, Atomic Force; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D056951:Photoelectron Spectroscopy; D010957:Plasmids; D035602:Transcriptional Elongation Factors / Q000235:genetics*; D014961:X-Ray Diffraction
chemical_list: D008055:Lipids; C108440:TCERG1 protein, human; D035602:Transcriptional Elongation Factors; D004247:DNA
keywords: Cationic solid lipid nanoparticles development; Cell viability; DNA binding efficiency; Plasmid DNA; Solid lipid nanoparticles characterization