Chitosan Hydrogel as siRNA vector for prolonged gene silencing

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  • Zhiwei Ma, State Key Laboratory of Military Stomatology, Department of Periodontology and Oral Medicine, The School of Stomatology, Fourth Military Medical University, Xi-an, China, China
  • Chuanxu Yang, State Key Laboratory of Military Stomatology, Department of Prothodontics, The School of Stomatology, Fourth Military Medical University, Xi-an, China, Denmark
  • Wen Song, State Key Laboratory of Military Stomatology, Department of Prothodontics, The School of Stomatology, Fourth Military Medical University, Xi-an, China, Denmark
  • Qintao Wang, State Key Laboratory of Military Stomatology, Department of Periodontology and Oral Medicine, The School of Stomatology, Fourth Military Medical University, Xi-an, China. qintaowang@hotmail.com., Unknown
  • Jørgen Kjems
  • Shan Gao, Denmark

BACKGROUND: The periodontitis is one of the most prevalent diseases with alveolar resorption in adult people and is the main cause of the tooth loss. To investigate the possibility for protecting the loss of alveolar bone in periodontal diseases, a RNAi-based therapeutic strategy is applied for silencing RANK signaling using thermosensitive chitosan hydrogel as siRNA reservoir and vector.

RESULTS: The thermosensitive chitosan hydrogel was formed from solution (PH = 7.2, at 4°C) at 37°C within 8 minutes. The degradation rates of hydrogel were ~50% and 5% (W remaining/W beginning) in the presence and absence of lysozyme, respectively, over a period of 20 days. The concurrent cumulative in vitro release of Cy3-labeled siRNA from the hydrogel was 50% and 17% over 14 days, with or without lysozyme digestion, respectively. High cell viability (>88%) was maintained for cells treated with hydrogel loaded with RANK specific siRNA and RANK knockdown was prolonged for up to 9 days when cells were incubated with siRNA/hydrogel complex. In vivo release of siRNA was investigated in a subcutaneous delivery setup in mice. The fluorescent signal from siRNA within hydrogel was remained for up to 14 days compared to less than one day for siRNA alone.

CONCLUSIONS: Chitosan hydrogel can potentially serve as a suitable reservoir and vector for local sustained delivery of siRNA in potential therapy.

Original languageEnglish
JournalJournal of Nanobiotechnology
Volume12
Issue23
Pages (from-to)1-9
Number of pages9
ISSN1477-3155
DOIs
Publication statusPublished - 19 Jun 2014

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