Solid lipid nanoparticles as non-viral vector for the treatment of chronic hepatitis C by RNA interference

[Display omitted] 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...

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Bibliographic Details
Published in:International journal of pharmaceutics 2015-02, Vol.479 (1), p.181-188
Main Authors: Torrecilla, Josune, del Pozo-Rodríguez, Ana, Apaolaza, Paola Stephanie, Solinís, María Ángeles, Rodríguez-Gascón, Alicia
Format: Article
Language:English
Subjects:
Cell Survival
Dextrans - chemistry
Genetic Vectors
HCV
Hep G2 Cells
Hepacivirus - genetics
Hepatitis C virus
Hepatitis C, Chronic - genetics
Hepatitis C, Chronic - therapy
Humans
Hyaluronan Receptors - metabolism
Hyaluronic acid
Hyaluronic Acid - chemistry
IRES
Lipids
Nanoparticles - administration & dosage
Protamines - chemistry
Ribosomes - genetics
Ribosomes - metabolism
RNA Interference
RNA, Small Interfering - administration & dosage
RNAi
shRNA
Solid lipid nanoparticles
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Summary:[Display omitted] 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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2014.12.047