title: Solid lipid nanoparticles as non-viral vector for the treatment of chronic hepatitis C by RNA interference.
abstract: RNA interference (RNAi) is a promising strategy to treat the chronic infection by hepatitis C virus (HCV). The objective of this work was to develop a non-viral vector based on solid lipid nanoparticles (SLN) and RNAi to inhibit the internal ribosome entry site (IRES) mechanism of the HCV. The vectors were prepared with SLN, protamine, hylauronic acid (HA) or dextran (DX), and a short-hairpin RNA expression plasmid targeted to the stem loop II of the 5' UTR (shRNA74). The particle size, surface charge, and capacity to bind, release and protect the shRNA74 against nucleases were evaluated. Cell uptake, silencing capacity and cell viability were evaluated in HepG2 cells. All the vectors presented particle size in the range of nanometers and positive surface charge, and they were able to protect the shRNA74 against DNase. An effective and rapid uptake into the cells was observed. Silencing capacity ranged from 3% to 67% depending on the presence of DX or HA in the vector, the shRNA74 to SLN ratio, and the shRNA74 dose. Vectors prepared with HA showed to be twice more effective than those prepared with DX. Differences in the intracellular trafficking may justify the higher efficacy of the HA-prepared vectors.
authors.affiliation: Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad, Vitoria-Gasteiz 701006, Spain. Electronic address: josune.torrecilla@ehu.es.
authors.forename: Josune
authors.initials: J
authors.lastname: Torrecilla
authors.affiliation: Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad, Vitoria-Gasteiz 701006, Spain. Electronic address: ana.delpozo@ehu.es.
authors.forename: Ana
authors.initials: A
authors.lastname: del Pozo-Rodríguez
authors.affiliation: Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad, Vitoria-Gasteiz 701006, Spain. Electronic address: paolastephanie.apaolaza@ehu.es.
authors.forename: Paola Stephanie
authors.initials: PS
authors.lastname: Apaolaza
authors.affiliation: Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad, Vitoria-Gasteiz 701006, Spain. Electronic address: marian.solinis@ehu.es.
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Solinís
authors.affiliation: Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad, Vitoria-Gasteiz 701006, Spain. Electronic address: alicia.rodriguez@ehu.es.
authors.forename: Alicia
authors.initials: A
authors.lastname: Rodríguez-Gascón
mesh_terms: D002470:Cell Survival; D003911:Dextrans / Q000737:chemistry; D005822:Genetic Vectors; D056945:Hep G2 Cells; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000628:therapy; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry; D008055:Lipids; D053758:Nanoparticles / Q000008:administration & dosage*; D011479:Protamines / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*
chemical_list: C497483:CD44 protein, human; D003911:Dextrans; D018960:Hyaluronan Receptors; D008055:Lipids; D011479:Protamines; D034741:RNA, Small Interfering; D006820:Hyaluronic Acid
keywords: HCV; Hyaluronic acid; IRES; RNAi; Solid lipid nanoparticles; shRNA