多柔比星热敏脂质体穿越血脑/血瘤屏障的研究

 目的 建立体外血脑屏障（blood-brain barrier, BBB）模型和体外血瘤屏障（blood-brain tumor barrier, BTB）模型,检测多柔比星两种剂型（thermosensitive liposome adriamycin, ts-lip-ADM和多柔比星溶液）在37 ℃/42 ℃条件下对两种模型的穿透性,为多柔比星热敏脂质体脑靶向药物递送研究奠定基础。方法 人脐静脉内皮细胞系ECV304和星形胶质细胞（Astrocytes, As）接触共培养建立共培养BBB模型;ECV304细胞和胶质瘤细胞系C6非接触共培养建立共培养BTB模型。测定模型的跨内皮阻抗值（trans-endothelial electrical resistance, TEER）和多柔比星通透性确证模型建立。建模第7天,测定多柔比星两种剂型在37 ℃/42 ℃条件下对两种模型的透过性（P_app）。结果 BBB模型的TEER值显著高于BTB模型,对ADM的透过量低于BTB模型。42 ℃加热条件下热敏脂质体在BBB和BTB模型中的药物透过量显著高于多柔比星溶液。结论 热敏脂质体结合加热处理可以显著促进多柔比星穿越体外血脑/血瘤屏障。

Investigation of Adriamycin Thermosensitive Liposomes Crossing the Blood-Brain Barrier and Blood-Brain Tumor Barrier

OBJECTIVE To investigate the penetration of thermosensitive liposomes loaded with adriamycin（ADM） across the blood-brain barrier (BBB) and blood-brain tumor barrier (BTB) in vitro models. METHODS ECV304 cells and astrocytes cells were co-cultivated on the two sides of semi-permeable PET filter for establishing a BBB model. The cultivation of ECV304 cells on the filter and C6 cells on the bottom of the plate generated a BTB model. The function of the two models were assessed by using the trans-endothelial electrical resistance (TEER). The penetration efficiency of adriamycin and thermosensitive liposomes adriamycin across BBB and BTB at 37 ℃ and 42 ℃ was tested respectively. RESULTS The value of TEER of BBB model was higher than that for BTB model under the same condition. Adriamycin penetrated across BTB more effectively than BBB. The adriamycin thermosensitive liposomes penetrated across either BBB or BTB more effectively than adriamycin alone at 42 ℃. CONCLUSION Thermosensitive liposomes of adriamycin combined with heating(42 ℃) can enhance the drug penetration across in vitro blood-brain barrier or blood-brain tumor barrier.