Chitosan Hydrogel as siRNA vector for prolonged gene silencing

Journal of Nanobiotechnology

Research

Chuanxu Yang¹  Shan Gao¹  Jørgen Kjems¹  Qintao Wang²  Zhiwei Ma²  Wen Song³ 

[1] Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Aarhus University, Gustav Wiedsvej 14, 8000, Aarhus C, Denmark;State Key Laboratory of Military Stomatology, Department of Periodontology and Oral Medicine, The School of Stomatology, Fourth Military Medical University, Xi-an, China;State Key Laboratory of Military Stomatology, Department of Prothodontics, The School of Stomatology, Fourth Military Medical University, Xi-an, China;

关键词: Chitosan;    Lysozyme;    Periodontitis;    Release Profile;    Alveolar Bone;   

DOI  :  10.1186/1477-3155-12-23

 received in 2014-01-18, accepted in 2014-06-04,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsThe 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.ConclusionsChitosan hydrogel can potentially serve as a suitable reservoir and vector for local sustained delivery of siRNA in potential therapy.

【 授权许可】

Unknown   
© Ma et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.