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Polymers 2017, 9(4), 142; doi:10.3390/polym9040142

Influence of Defined Hydrophilic Blocks within Oligoaminoamide Copolymers: Compaction versus Shielding of pDNA Nanoparticles

1
Department of Pharmacy, Pharmaceutical Biotechnology, Ludwig-Maximilians-Universität München, 81377 München, Germany
2
Department of Internal Medicine IV, University Hospital, Ludwig-Maximilians-Universität München, 81377 München, Germany
3
Department of Physics, Ludwig-Maximilians-Universität München, 80799 München, Germany
4
Department of Physics, and Center for NanoScience (CeNS), Ludwig-Maximilians-Universität München, 80799 München, Germany
5
Department of Pharmacy, Pharmaceutical Biotechnology, and Center for NanoScience (CeNS), Ludwig-Maximilians-Universität München, 81377 München, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Ravin Narain
Received: 15 March 2017 / Revised: 7 April 2017 / Accepted: 11 April 2017 / Published: 19 April 2017
(This article belongs to the Special Issue Polymers and Nanogels for Gene Therapy)
View Full-Text   |   Download PDF [2680 KB, uploaded 19 April 2017]   |  

Abstract

Cationic polymers are promising components of the versatile platform of non-viral nucleic acid (NA) delivery agents. For a successful gene delivery system, these NA vehicles need to comprise several functionalities. This work focuses on the modification of oligoaminoamide carriers with hydrophilic oligomer blocks mediating nanoparticle shielding potential, which is necessary to prevent aggregation or dissociation of NA polyplexes in vitro, and hinder opsonization with blood components in vivo. Herein, the shielding agent polyethylene glycol (PEG) in three defined lengths (12, 24, or 48 oxyethylene repeats) is compared with two peptidic shielding blocks composed of four or eight repeats of sequential proline-alanine-serine (PAS). With both types of shielding agents, we found opposing effects of the length of hydrophilic segments on shielding and compaction of formed plasmid DNA (pDNA) nanoparticles. Two-arm oligoaminoamides with 37 cationizable nitrogens linked to 12 oxyethylene units or four PAS repeats resulted in very compact 40–50 nm pDNA nanoparticles, whereas longer shielding molecules destabilize the investigated polyplexes. Thus, the balance between sufficiently shielded but still compact and stable particles can be considered a critical optimization parameter for non-viral nucleic acid vehicles based on hydrophilic-cationic block oligomers. View Full-Text
Keywords: complex stability; nanoparticle; oligoamine; nucleic acid delivery; plasmid DNA (pDNA); polyethylene glycol (PEG); polyplex; shielding complex stability; nanoparticle; oligoamine; nucleic acid delivery; plasmid DNA (pDNA); polyethylene glycol (PEG); polyplex; shielding
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Morys, S.; Krhac Levacic, A.; Urnauer, S.; Kempter, S.; Kern, S.; Rädler, J.O.; Spitzweg, C.; Lächelt, U.; Wagner, E. Influence of Defined Hydrophilic Blocks within Oligoaminoamide Copolymers: Compaction versus Shielding of pDNA Nanoparticles. Polymers 2017, 9, 142.

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