3 years ago

Cationic Nanohydrogel Particles for Therapeutic Oligonucleotide Delivery

Cationic Nanohydrogel Particles for Therapeutic Oligonucleotide Delivery
Rudolf Zentel, Lutz Nuhn, Nadine Leber
Short pharmaceutical active oligonucleotides such as small interfering RNA (siRNA) or cytidine-phosphate-guanosine (CpG) are considered as powerful therapeutic alternatives, especially to medicate hard-to-treat diseases (e.g., liver fibrosis or cancer). Unfortunately, these molecules are equipped with poor pharmacokinetic properties that prevent them from translation. Well-defined nanosized carriers can provide opportunities to optimize their delivery and guide them to their site of action. Among several concepts, this Feature Article focuses on cationic nanohydrogel particles as a universal delivery system for small anionic molecules including siRNA and CpG. Cationic nanohydrogels are derived from preaggregated precursor block copolymers, which are further cross-linked to obtain well-defined nanoparticles of tunable sizes and with (degradable) cationic cores. Novel opportunities for oligonucleotide delivery in vitro and in vivo with respect to liver fibrosis therapies will be highlighted as well as perspectives toward modulating the immune system. In general, the approach of covalently stabilized cationic carrier systems can contribute to find advanced oligonucleotide therapeutics. To medicate hard-to-treat diseases like liver fibrosis or cancer by short pharmaceutical active oligonucleotides (e.g., small interfering RNA or cytidine-phosphate-guanosine), well-defined nanosized carriers are required to facilitate delivery to their site of action. This article summarizes the recent progress of cationic nanohydrogel particles derived from preaggregated precursor block copolymers for such purposes.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/mabi.201700092

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