聚合物纳米胶束增溶靛玉红增强抗白血病疗效的研究

项目名称： 聚合物纳米胶束增溶靛玉红增强抗白血病疗效的研究

项目编号： No.20874032

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 蒋刚彪

作者单位： 华南农业大学

项目金额： 33万元

中文摘要： 以壳聚糖为基本原料，通过对壳聚糖进行结构修饰，设计了四种两亲性壳聚糖衍生物，予以合成制备了四种壳聚糖衍生物纳米胶束，并详细表征了衍生物的分子结构，研究了它们的自聚集行为和药物负载能力，考察了它们的生物安全性，血液相容性，同时考察了它们对靛玉红的增溶控释能力，探讨了聚合物胶束负载靛玉红的药代动力学行为，开展了增溶控释靛玉红对白血病细胞的杀伤能力以及对靛玉红治疗慢粒白血病 (CML)疗效的提高能力的研究。研究结果显示，所制备的壳聚糖衍生物有较好的药物负载和增溶控释能力，N-软脂酰基壳聚糖（PLCS）增溶靛玉红后，对血药浓度提高了2倍多，对白血病细胞的杀伤力提高了近两倍，研究证实聚合物胶束增溶控释靛玉红不啻为一个改善靛玉红水溶性和疗效的一个好办法。在基金资助下，申请人针对两亲性壳聚糖衍生物胶束的研究发表了IF 5.09的SCI 论文1篇，IF 3.45的SCI 论文2篇，中文核心期刊2篇，此外还有多篇SCI 论文在审稿之中。

中文关键词： 聚合物胶束；壳聚糖；药物控制释放；靛玉红；白血病

英文摘要： Four kinds of amphiphilic chitosan derivatives were synthesized by modification of chitosan, and four kinds of polymeric micelles were obtained through the self-assembly of the amphiphilic chitosan derivatives dissolved in water. The molecular structure of the derivatives was characterized detailedly, and the self-aggregation behavior and drug-loading capacity were studied. The biocompatibility and blood compatibility were investigated as well. Especially, the solubilization and drug controlled release of indirubin by polymer micelles based on chitosan derivatives were deeply studied. The pharmacokinetics of indirubin loading by chitosan derivatives based polymer micelles were studied, and leukaemia cell cytotoxicity of solubilized indirubin and the effectiveness increase of solubilized indirubin treating chronic myelogenous leukemia (CML) were studied. The study result revealed that the prepared polymer micelles based on chitosan derivatives have excellent indirubin drug loading capacity and solubilization. The loading capacity of PLCS –oaded indirubin approximately reached 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 and the treatment outcome of leukaemia.

英文关键词： polymer micelle; chitosan; drug controlled release; indirubin; leukemia