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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(Papp)。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。
OBJECTIVE To establish a model of blood-brain barrier (BBB) and a model of blood-brain tumor barrier (BTB) in vitro and to detect the effects of thermosensitive liposome adriamycin Doxorubicin solution) penetrated both models at 37 ° C / 42 ° C, laying a foundation for the study of doxorubicin thermosensitive liposomal brain-targeting drug delivery. Methods Co-culture BBB model was established by co-culture of human umbilical vein endothelial cell line ECV304 and Astrocytes (As). The co-cultured BTB model was established by non-contact co-culture of ECV304 cells and C6 glioma cells. The trans-endothelial electrical resistance (TEER) and doxorubicin permeability confirmatory models were established. On the 7th day of modeling, the two formulations of doxorubicin were tested for Papp on both models at 37 ° C / 42 ° C. Results The TEER value of BBB model was significantly higher than that of BTB model, and the transdermal penetration of ADM was lower than that of BTB model. Thermosensitive liposomes at 42 ℃ heated in BBB and BTB model drug penetration was significantly higher than doxorubicin solution. Conclusion Thermal liposomes combined with heat treatment can significantly promote doxorubicin crossing blood-brain / blood-borne barrier in vitro.