论文部分内容阅读
大多数抗肿瘤药物难以穿透血脑屏障(BBB)因而无法用于脑胶质瘤的治疗。葡萄糖转运体(GLUTs)在血脑屏障和脑胶质瘤细胞上均有高度表达,这使得葡萄糖转运体相关配体修饰的药物载体跨越血脑屏障、靶向脑胶质瘤细胞成为可能。本研究之目的在于合成一种新的葡萄糖转运体配体靶向材料TPGS_(1000)-Glu、制备TPGS_(1000)-Glu修饰的表阿霉素脂质体,并评价该脂质体制剂的药物效应。评价方法主要在体外血脑屏障共培养模型和脑胶质瘤细胞上进行。TPGS_(1000)-Glu以TPGS_(1000)-COOH和4-氨基苯基-β-D-吡喃葡萄糖苷(Glu)为原料进行合成。基质辅助激光解析电离飞行时间质谱(MALDI-TOF-MS)验证结果显示,试验成功的合成了TPGS_(1000)-Glu。研制的TPGS_(1000)-Glu修饰表阿霉素脂质体具有包封率高(>97%)、纳米粒径(~90nm)、在含血清缓冲体系中药物泄漏少等理化特征。本研究还建立了血脑屏障与脑胶质瘤共培养模型,在该模型中加入TPGS_(1000)-Glu修饰表阿霉素脂质体后,该脂质体药物表现出明显的跨越血脑屏障效应、并在跨越血脑屏障后表现出较强的脑胶质瘤细胞摄取效应及抗脑胶质瘤效应。因此,合成的TPGS_(1000)-Glu为血脑屏障提供了一种新的靶向配体,而所制备的TPGS_(1000)-Glu修饰表阿霉素脂质体则为脑胶质瘤治疗提供了一种有潜力的抗肿瘤制剂。
Most anti-tumor drugs are difficult to penetrate the blood-brain barrier (BBB) and therefore can not be used for the treatment of glioma. Glucose transporters (GLUTs) are highly expressed on the blood-brain barrier and glioma cells, making it possible for drug carriers modified by glucose transporter-related ligands to cross the blood-brain barrier and target glioma cells. The purpose of this study was to synthesize TPGS_ (1000) -Glu, a new glucose transporter ligand targeting material, to prepare TPGS_ (1000) -Glu modified epirubicin liposomes and evaluate the effect of Drug effect. The evaluation method is mainly carried out on in vitro blood-brain barrier co-culture model and glioma cells. TPGS_ (1000) -Glu was synthesized by using TPGS_ (1000) -COOH and 4-aminophenyl-β-D-glucopyranoside (Glu) as raw materials. Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) verification results show that the successful synthesis of the TPGS_ (1000) -Glu. The developed TPGS_ (1000) -Glu modified epirubicin liposomes have the characteristics of high encapsulation efficiency (> 97%), nanoparticle size (~ 90nm), less drug leakage in the serum-containing buffer system. This study also established a model of co-culture of blood brain barrier and glioma. After adding TPGS_ (1000) -Glu modified epirubicin liposome into the model, the liposomal drug showed a clear cross across the blood brain Barrier effect, and showed strong glioma uptake and anti-glioma effect after crossing the blood-brain barrier. Therefore, the synthetic TPGS_ (1000) -Glu provides a new targeting ligand for the blood-brain barrier, whereas the prepared TPGS_ (1000) -Glu modified epirubicin liposomes are treated by glioma Provides a potential antitumor agent.