Affiliation:
1. Laboratory of Organic and Macromolecular Chemistry (IOMC) Friedrich Schiller University Jena Humboldtstrasse 10 07743 Jena Germany
2. Institute of Bioprocess Engineering and Pharmaceutical Technology University of Applied Sciences Mittelhessen Wiesenstrasse 14 35390 Giessen Germany
3. Jena Center for Soft Matter (JCSM) Friedrich Schiller University Jena Philosophenweg 7 07743 Jena Germany
Abstract
AbstractCationic pH‐responsive polymers promise to overcome critical challenges in cellular delivery. Ideally, the polymers become selectively charged along the endosomal pathway disturbing only the local membrane and avoiding unintended interactions or cytotoxic side effects at physiological conditions. Polypiperazines represent a novel, hydrophilic class of pH‐responsive polymers whose response can be tuned within the relevant pH range (5–7.4). The authors discovered that the polypiperazines are effectively binding plasmid DNA (pDNA) and demonstrate high efficiency in transfection. By design of experiments (DoE), a wide parameter space (pDNA and polymer concentration) is screened to identify the range of effective concentrations for transfection. An isopropyl modified polypiperazine is highly efficient over a wide range of concentrations outperforming linear polyethylenimine (l‐PEI, 25 kDa) in regions of low N*/P ratios. A quantitative polymerase chain reaction (qPCR) surprisingly revealed that the pDNA within the piperazine‐based polyplexes can be amplified in contrast to polyplexes based on l‐PEI. The pDNA must therefore be more accessible and bound differently than for other known transfection polymers. Considering the various opportunities to further optimize their structure, polypiperazines represent a promising platform for designing effective soluble polymeric vectors, which are charge‐neutral at physiological conditions.
Funder
Hessisches Ministerium für Wissenschaft und Kunst
Deutsche Forschungsgemeinschaft
Bundesministerium für Bildung und Forschung
Subject
Materials Chemistry,Polymers and Plastics,Biomaterials,Bioengineering,Biotechnology
Cited by
3 articles.
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