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Open AccessArticle

Highly Effective Non-Viral Antitumor Gene Therapy System Comprised of Biocompatible Small Plasmid Complex Particles Consisting of pDNA, Anionic Polysaccharide, and Fully Deprotected Linear Polyethylenimine

1
Japan Anti-tuberculosis Association, Shin-Yamanote Hospital, 3-6-1 Suwa-cho, Higashimurayama, Tokyo 189-0021, Japan
2
Graduate School of Life and Environmental Sciences, Osaka Prefecture University 1-58 Rinku-oraikita, Izumisano, Osaka 598-8531, Japan
3
Department of Home Economics, Otsuma Women's University, 12 Sanbancho, Chiyoda-ku, Tokyo 102-8357, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Keiji Itaka
Pharmaceutics 2015, 7(3), 152-164; https://doi.org/10.3390/pharmaceutics7030152
Received: 31 May 2015 / Revised: 10 July 2015 / Accepted: 17 July 2015 / Published: 23 July 2015
(This article belongs to the Special Issue New Paradigm of Gene Therapy)
We have reported that ternary complexes of plasmid DNA with conventional linear polyethylenimine (l-PEI) and certain polyanions were very stably dispersed, and, with no cryoprotectant, they could be freeze-dried and re-hydrated without the loss of transfection ability. These properties enabled the preparation of a concentrated suspension of very small pDNA complex, by preparing the complexes at highly diluted conditions, followed by condensation via lyophilization-and-rehydration procedure. Recently, a high potency linear polyethylenimine having no residual protective groups, i.e., Polyethylenimine “Max” (PEI “Max”), is available, which has been reported to induce much higher gene expression than conventional l-PEI. We tried to prepare the small DNA/PEI “Max”/polyanion complexes by a similar freeze-drying method. Small complex particles could be obtained without apparent aggregation, but transfection activity of the rehydrated complexes was severely reduced. Complex-preparation conditions were investigated in details to achieve the freeze-dried DNA/PEI “Max”/polyanion small ternary complexes with high transfection efficiency. DNA/PEI “Max”/polyanion complexes containing cytokine-coding plasmids were then prepared, and their anti-tumor therapeutic efficacy was examined in tumor-bearing mice. View Full-Text
Keywords: non-viral; transfection; plasmid; Polyethylenimine “Max”; freeze-drying; hyaluronic acid; chondroitin sulfate; antitumor; cytokine; nanoparticle non-viral; transfection; plasmid; Polyethylenimine “Max”; freeze-drying; hyaluronic acid; chondroitin sulfate; antitumor; cytokine; nanoparticle
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Koyama, Y.; Sugiura, K.; Yoshihara, C.; Inaba, T.; Ito, T. Highly Effective Non-Viral Antitumor Gene Therapy System Comprised of Biocompatible Small Plasmid Complex Particles Consisting of pDNA, Anionic Polysaccharide, and Fully Deprotected Linear Polyethylenimine. Pharmaceutics 2015, 7, 152-164.

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