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Int J Pharm. 2017 Feb 25;518(1-2):66-79. doi: 10.1016/j.ijpharm.2016.12.048. Epub 2016 Dec 23.

Efficient gene delivery to primary human retinal pigment epithelial cells: The innate and acquired properties of vectors.

Author information

1
Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran. Electronic address: n_tasharrofi@yahoo.com.
2
Stem Cell Technology Research Center, Tehran, Iran. Electronic address: f.kouhkan@stemcellstech.com.
3
Department of Hematology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran. Electronic address: soleim_m@modares.ac.ir.
4
Institute of Medical Biotechnology, Faculty of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. Electronic address: soheili@nigeb.ac.ir.
5
Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran; Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
6
Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran. Electronic address: akbarijo@tums.ac.ir.
7
Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran; Medical Biomaterial Research Center (MBRC), Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran. Electronic address: dorkoosh@tums.ac.ir.

Abstract

The purpose of this study is designing non-viral gene delivery vectors for transfection of the primary human retinal pigment epithelial cells (RPE). In the design process of gene delivery vectors, considering physicochemical properties of vectors alone does not seem to be enough since they interact with constituents of the surrounding environment and hence gain new characteristics. Moreover, due to these interactions, their cargo can be released untimely or undergo degradation before reaching to the target cells. Further, the characteristics of cells itself can also influence the transfection efficacy. For example, the non-dividing property of RPE cells can impede the transfection efficiency which in most studies was ignored by using immortal cell lines. In this study, vectors with different characteristics differing in mixing orders of pDNA, PEI polymer, and PLGA/PEI or PLGA nanoparticles were prepared and characterized. Then, their characteristics and efficacy in gene delivery to RPE cells in the presence of vitreous or fetal bovine serum (FBS) were evaluated. All formulations showed no cytotoxicity and were able to protect pDNA from premature release and degradation in extracellular media. Also, the adsorption of vitreous or serum proteins onto the surface of vectors changed their properties and hence cellular uptake and transfection efficacy.

KEYWORDS:

PLGA/PEI nanoparticles; Primary human RPE cells; Protein adsorption; Transfection; Vitreous

PMID:
28017770
DOI:
10.1016/j.ijpharm.2016.12.048
[Indexed for MEDLINE]

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