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Merck
  • Chitosan nanoparticles for siRNA delivery: optimizing formulation to increase stability and efficiency.

Chitosan nanoparticles for siRNA delivery: optimizing formulation to increase stability and efficiency.

Journal of controlled release : official journal of the Controlled Release Society (2014-01-07)
H Ragelle, R Riva, G Vandermeulen, B Naeye, V Pourcelle, C S Le Duff, C D'Haese, B Nysten, K Braeckmans, S C De Smedt, C Jérôme, V Préat
摘要

This study aims at developing chitosan-based nanoparticles suitable for an intravenous administration of small interfering RNA (siRNA) able to achieve (i) high gene silencing without cytotoxicity and (ii) stability in biological media including blood. Therefore, the influence of chitosan/tripolyphosphate ratio, chitosan physicochemical properties, PEGylation of chitosan as well as the addition of an endosomal disrupting agent and a negatively charged polymer was assessed. The gene silencing activity and cytotoxicity were evaluated on B16 melanoma cells expressing luciferase. We monitored the integrity and the size behavior of siRNA nanoparticles in human plasma using fluorescence fluctuation spectroscopy and single particle tracking respectively. The presence of PEGylated chitosan and poly(ethylene imine) was essential for high levels of gene silencing in vitro. Chitosan nanoparticles immediately released siRNA in plasma while the inclusion of hyaluronic acid and high amount of poly(ethylene glycol) in the formulation improved the stability of the particles. The developed formulations of PEGylated chitosan-based nanoparticles that achieve high gene silencing in vitro, low cytotoxicity and high stability in plasma could be promising for intravenous delivery of siRNA.

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Chitosan-mPEG 1k, 25-60% PEGylation, medium MW
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