Effect of Chitosan Properties on Immunoreactivity.
Effect of Chitosan Properties on Immunoreactivity.
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DOI：
10.3390/md14050091
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发表时间：
2016-05-11
期刊：
影响因子：
5.4
通讯作者：
Zaharoff DA
中科院分区：
文献类型：
--
作者：
Ravindranathan S;Koppolu BP;Smith SG;Zaharoff DA
壳聚糖是一种广泛应用于药物和基因传递、组织工程和疫苗开发的生物聚合物。然而，由于文献中关于壳聚糖免疫反应性的矛盾结果，对壳聚糖的免疫反应尚不清楚。因此，在本研究中，我们分析了各种生化特性，即去乙酰化程度（DDA），粘度/聚合物长度和内毒素水平，对抗原提呈细胞（APCs）免疫反应的影响。将不同来源的壳聚糖溶液分别用小鼠和人apc（巨噬细胞和/或树突状细胞）处理，并以细胞释放的肿瘤坏死因子-α (TNF-α)量作为免疫反应性指标。我们的研究结果表明，只有内毒素含量而不是DDA或粘度影响壳聚糖诱导的免疫反应。我们的数据还表明，低内毒素壳聚糖（<0.01 EU/mg）在20 ~ 600 cP和80% ~ 97% DDA范围内基本上是惰性的。本研究强调，为了使壳聚糖这种有价值的生物材料得到广泛的临床应用，需要在临床前研究中对其进行更完整的表征和纯化。
Chitosan is a widely investigated biopolymer in drug and gene delivery, tissue engineering and vaccine development. However, the immune response to chitosan is not clearly understood due to contradicting results in literature regarding its immunoreactivity. Thus, in this study, we analyzed effects of various biochemical properties, namely degree of deacetylation (DDA), viscosity/polymer length and endotoxin levels, on immune responses by antigen presenting cells (APCs). Chitosan solutions from various sources were treated with mouse and human APCs (macrophages and/or dendritic cells) and the amount of tumor necrosis factor-α (TNF-α) released by the cells was used as an indicator of immunoreactivity. Our results indicate that only endotoxin content and not DDA or viscosity influenced chitosan-induced immune responses. Our data also indicate that low endotoxin chitosan (<0.01 EU/mg) ranging from 20 to 600 cP and 80% to 97% DDA is essentially inert. This study emphasizes the need for more complete characterization and purification of chitosan in preclinical studies in order for this valuable biomaterial to achieve widespread clinical application.