Investigation of polyethylenimine-grafted-triamcinolone acetonide as nucleus-targeting gene delivery systems

The Journal of Gene Medicine
Kun MaYi Jin

Abstract

Nuclear membrane is one of the main barriers in polymer mediated intracellular gene delivery. To improve the transgenic activity and safety of nonviral vector, triamcinolone acetonide (TA) as a nuclear localization signal was conjugated with different molecular weight polyethylenimine (PEI). Different molecular weight PEI [600, 1800, 25,000 (25k)] was conjugated with TA to synthesize PEI-TA by two-step reaction. Their physicochemical characteristics, in vitro cytotoxicity and transfection efficiency were evaluated. To investigate the difference of transfection efficiency of various molecular weight PEI-TA, their transfection mechanism was further investigated by confocal microscopy and competition assay. Transgenic expression in vivo was evaluated by injection into hepatic portal vein of mice. All PEI-TA could form nanosize polyplexes with DNA and their physicochemical properties resemble each other. Their cytotoxicities were negligible compared to PEI 25k. The order of transfection efficiency was PEI 1800-TA > PEI 600-TA > PEI 25k-TA. A transfection mechanism study displayed that TA could inhibit considerably the transgenic activity of PEI 1800-TA and PEI 600-TA, but that of PEI 25k-TA was not inhibited. It was suggested that ...Continue Reading

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Citations

Jan 13, 2011·Pharmaceutical Research·Francisco C Pérez-MartínezValentín Ceña
Feb 1, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Forrest M KievitMiqin Zhang
Apr 4, 2021·Biomedicines·Natallia V DubashynskayaYury A Skorik

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