| Dextran and protamine-based solid lipid nanoparticles as potential vectors for the treatment of X linked juvenile retinoschisis. | |
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MedLine Citation:
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PMID: 22295905 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The aim of the present study was to analyze the potential application of non-viral vectors based on solid lipid nanoparticles (SLN) for the treatment of ocular diseases by gene therapy, specifically X linked juvenile retinoschisis (XLRS). Vectors were prepared with SLN, dextran, protamine, and a plasmid (pCMS-EGFP or pCEP4-RS1). Formulations were characterized and the "in vitro" transfection capacity as well as the cellular uptake and the intracellular trafficking were studied in ARPE-19 cells. Formulations were also tested in vivo in Wistar rat eyes and the efficacy was studied by monitoring the expression of EGFP after intravitreal, subretinal and topical administration. The presence of dextran and protamine in the SLN improved greatly the expression of retinoschisin and green fluorescent protein in ARPE-19. The nuclear localization signals (NLS) of protamine, its protection capacity and a shift in the internalization mechanism from caveolae-mediated to clathrin-mediated endocytosis promoted by the dextran, justify the increase of transfection. After ocular administration of the dextran-protamine-DNA-SLN complex to the rat eyes, we detected the expression of EGFP in various types of cells depending on the administration route. Our vectors were also able to transfect corneal cells after topical application. We have demonstrated the potential utility of our non-viral vectors loading XLRS1 plasmid and provided evidence for their potential application for the treatment of degenerative retina disorders as well as ocular surface diseases. |
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Authors:
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Diego Delgado; Ana Del Pozo-Rodríguez; Maria Ángeles Solinís; Marcelino Avilés; Bernhard Hf Weber; Eduardo Fernández; Alicia Rodríguez Gascón |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-1 |
Journal Detail:
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Title: Human gene therapy Volume: - ISSN: 1557-7422 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9008950 Medline TA: Hum Gene Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of the Basque Country, Pharmacy and Pharmaceutical Technology, Vitoria-Gasteiz, Alava, Spain; diego.delgado@ehu.es. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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