Cholic acid modified N-(2-hydroxy)-propyl-3-trimethylammonium chitosan chloride for superoxide dismutase delivery
Cholic acid modified N-(2-hydroxy)-propyl-3-trimethylammonium chitosan chloride for superoxide dismutase delivery
复制标题
用于超氧化物歧化酶递送的胆酸修饰的 N-(2-羟基)-丙基-3-三甲基氯化铵壳聚糖
DOI：
10.1016/j.ijpharm.2013.06.056
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发表时间：
2013-09-15
影响因子：
5.8
通讯作者：
Yao, Ping
中科院分区：
文献类型：
--
作者：
Cheng, Ye;Cai, Huanxin;Yao, Ping
本研究合成了一系列新型两亲性壳聚糖衍生物--胆酸改性的N-（2-羟基）-丙基-3-三甲基氯化铵壳聚糖（HTCC-CA），并对其季铵化程度和胆酸取代度进行了研究。HTCC-CA具有生物相容性，并在水溶液中形成颗粒。超氧化物歧化酶（SOD）在pH 6.8的结合破坏了HTCC-CA的原始聚集体，并通过静电和疏水相互作用产生更小的SOD/HTCC-CA复合物纳米颗粒。HTCC-CA对SOD的负载效率和负载量分别达到90%和45%以上。激光共聚焦扫描显微镜观察和流式细胞仪分析表明，SOD/HTCC-CA复合纳米粒极大地增强了负载SOD的细胞内化。通过测定静脉注射游离SOD、游离HTCC-CA和SOD/HTCC-CA纳米粒后大鼠血清和脏器中SOD活性和丙二醛浓度，评价其体内抗氧化效果。结果表明，游离HTCC-CA是有效的清除超氧阴离子自由基在血液循环和SOD/HTCC-CA纳米粒子具有更好的抗氧化效率比游离SOD和游离HTCC-CA。(C)2013 Elsevier B. V.保留所有权利。
A series of novel amphiphilic chitosan derivatives, cholic acid modified N-(2-hydroxy)-propyl-3-trimethylammonium chitosan chloride (HTCC-CA) with different quaternization degrees and cholic acid substitutions were synthesized in this study. HTCC-CA is biocompatible and forms particles in aqueous solution. The binding with superoxide dismutase (SOD) at pH 6.8 destroys the original aggregates of HTCC-CA and produces smaller SOD/HTCC-CA complex nanoparticles via electrostatic and hydrophobic interactions. The SOD loading efficiency and loading capacity of HTCC-CA can reach to more than 90% and 45%, respectively. Confocal laser scanning microscopy observation and flow cytometry analysis reveal that SOD/HTCC-CA complex nanoparticles greatly enhance the cellular internalization of the loaded SOD. The SOD activities and malonaldehyde concentrations in the serum and organs of the rats, administrated intravenously with free SOD, free HTCC-CA, and SOD/HTCC-CA nanoparticles, were assayed to evaluate the antioxidant efficiency in vivo. The results demonstrate that free HTCC-CA is effective to scavenge superoxide radicals in the blood circulation and SOD/HTCC-CA nanoparticles have better antioxidant efficiency than free SOD as well as free HTCC-CA. (C) 2013 Elsevier B.V. All rights reserved.