Chitosan (CS) shows in vitro and in vivo efficacy for siRNA delivery but with contradictory findings for incompletely characterized systems. For understanding which parameters produce effective delivery, a library of precisely characterized chitosans was produced at different degrees of deacetylation (DDAs) and average molecular weights (M_n). Encapsulation and transfection efficiencies were characterized in vitro. Formulations were selected to examine the influence of M_n and N:P ratio on nanoparticle uptake, metabolic activity, genotoxicity, and in vitro transfection. Hemocompatibility and in vivo biodistribution were then investigated for different M_n, N:P ratios, and doses. Nanoparticle uptake and gene silencing correlated with increased surface charge, which was obtained at high DDA and high M_n. A minimum polymer length of ∼60–70 monomers (∼10 kDa) was required for stability and knockdown. In vitro knockdown was equivalent to lipid control with no metabolic or genotoxicity. An inhibitory effect of serum on biological performance was dependent on DDA, M_n, and N:P. In vivo biodistribution in mice show accumulation of nanoparticles in kidney with 40–50% functional knockdown.

中文翻译：

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siRNA与壳聚糖的传递：壳聚糖分子量，脱乙酰度和胺与磷酸盐的比例对体外沉默效率，血液相容性，生物分布和体内功效的影响。

壳聚糖（CS）显示了siRNA递送的体外和体内功效，但对于表征不完全的系统却存在矛盾的发现。为了了解哪些参数可有效递送，在不同的脱乙酰度（DDA）和平均分子量（M _n）下，制备了精确表征的壳聚糖库。封装和转染效率进行了体外表征。选择制剂以检查M _n和N：P比对纳米颗粒摄取，代谢活性，遗传毒性和体外转染的影响。然后研究不同M _n的血液相容性和体内生物分布，N：P比例和剂量。纳米颗粒的吸收和基因沉默与表面电荷的增加相关，这是在高DDA和高M _{n下获得的}。稳定和击倒至少需要60〜70个单体（〜10 kDa）的聚合物长度。体外敲除相当于没有代谢或遗传毒性的脂质控制。对生物性能血清的抑制效果依赖于DDA，中号_Ñ，和N：P。小鼠体内的生物分布显示肾脏中纳米颗粒的堆积，功能击倒率为40％至50％。