Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 360, Issue 1-2, Pages 177-183Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2008.04.023
Keywords
solid lipid nanoparticles; transfection; intracellular trafficking; ARPE-19 cells; Caveolae; clathrin
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Funding
- Spanish Ministry of Education and Science [AP2003-4780]
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Retinal pigment epithelial (RPE) cells are usually employed to study DNA systems for diseases related to problems in the retina. Solid lipid nanoparticles (SLNs) have been shown to be useful non-viral vectors for gene therapy. The objective of this work was to evaluate the transfection capacity of SLNs in the human retinal pigment epithelial established cell line (ARPE-19) in order to elucidate the potential application of this vector in the treatment of retinal diseases. Results showed a lower transfection level of SLNs in ARPE19 cells than in HEK293 (2.5% vs. 14.9% EGFP positive cells at 72 h post-transfection). Trafficking studies revealed a delay in cell uptake of the vectors in ARPE-19 cells. Differences in internalization process into the two cell lines studied explain, in part, the difference in the gene expression. The clathrin-mediated endocytosis in ARPE-19 cells directs the solid lipid nanoparticles to lysosomes; moreover, the low division rate of this cell line hampers the entrance of DNA into the nucleus. The knowledge of intracellular trafficking is very useful in order to design more efficient vectors taking into account the characteristics of the specific cell line to be transfected. (c) 2008 Elsevier B.V. All rights reserved.
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