N-软脂酰基壳聚糖的制备及其改善靛玉红水溶性的药动学研究  

Preparation of N-palmitoyl chitosan and improvement of pharmacokinetics of indirubin

作　　者：王来友[1] 蒋刚彪[2] 方羽生[2] 巫玮[1] 臧林泉[1] 曾明华[3] 

机构地区：[1]广东药学院药科学院,广东广州510006 [2]华南农业大学制药工程系,广东广州510642 [3]广西师范大学药用资源化学与药物分子工程教育部重点实验室,广西桂林541004

出　　处：《广东药学院学报》2009年第1期7-10,共4页Academic Journal of Guangdong College of Pharmacy

基　　金：国家自然科学基金(20874032);广东省教育部产学研资助项目(2006D90501003);广西师范大学药用资源化学与药物分子工程教育部重点实验室开放基金(桂科能0630006-5D07)

摘　　要：目的制备N-软脂酰基壳聚糖(PLCS)纳米胶束,改善难溶性药物靛玉红的溶解性与生物利用度。方法首先使用溶胀的壳聚糖与软脂酸酐在二甲基亚砜溶剂中反应合成水溶性的PLCS,通过IR和1H-NMR表征PLCS的结构;然后用其负载靛玉红,以激光散射和透射电镜检测载药纳米胶束的物理特征,用HPLC法测定其包封率。最后进行载药纳米胶束腹腔注射给药后在大鼠体内的药动学实验,与靛玉红混悬剂对照。结果合成得到的PLCS能很好地负载并增溶靛玉红,载药率可达10%左右。药动学研究表明,用PLCS载靛玉红后较靛玉红混悬剂的AUC提高了2.21倍,显著提高了靛玉红在大鼠体内的生物利用度。结论PLCS可作为提高难溶性药物靛玉红生物利用度的有效载体,进而可能改善靛玉红治疗白血病的疗效。Objective To prepare N-palmitoyl chitosan（PLCS） nanomicells for improving the solubility and bioavailability of water-insoluble indirubin. Methods The water-soluble PLCS was synthesized by swollen chitosan reacting with palmitic anhydride in dimethyl sulfoxide , then it was used to encapsulate indirubin. PLCS was characterized by IR and ^1 H-NMR. The loadingcapacity of indirubin-loaded PLCS was evaluated by HPLC. Pharrnacokinetics of indirubin-loaded PLCS in rat in vivo was compared with that of indirubin suspension. Results PLCS was well prepared and indirubin was loaded in PLCS micelles, The loading capacity of PLCS-loaded iodirubin was approximately 10%. Pharmacokinetics showed that the area under curve （ AUC ） of PLCS-loaded indirubin was two times higher than that of indirubin suspension. PLCS increased greatly the bioavailability of indirubin. Conclusion PLCS would be an effective carrier as the water-insoluble indirubin through increasing its bioavailability in the treatment of leukaemia.

关 键 词：靛玉红 N-软脂酰基壳聚糖 纳米胶束 药动学 

分 类 号：TQ460.3[化学工程—制药化工] R96[医药卫生—药理学]