Kakinuma K, Tanaka R, Takahashi H, Sekihara Y, Watanabe M, Kuroki M
Department of Neurosurgery, Niigata University, Japan.
Int J Hyperthermia. 1996 Jan-Feb;12(1):157-65. doi: 10.3109/02656739609023698.
We investigated the possibilities of drug delivery to the brain using thermosensitive liposomes and hyperthermia. Thermosensitive liposomes are small vesicles containing some drugs, which are designed to release the drugs in response to hyperthermia. The first experiment consisted of four groups: (1) received free Cisplatin: cis-diamminedichloroplatinum (CDDP); (2) received free CDDP and above 41 degrees C local brain heating for 30 min; (3) received liposomes containing CDDP (CDDP-liposome); and (4) received CDDP-liposome and above 41 degrees C local brain heating for 30 min. Brain CDDP levels were significantly higher in (4), while those on the other groups were undetectable. In the second experiment, we studied the distribution of Evans blue (Eb) in the artificially heated region of mongrel dogs' brain. One group received free Eb and the other group received liposomes containing Eb (Eb-liposome). While the extravasation of free Eb was localized in regions heated > 44 degrees C, that of Eb-liposome was extended up to the regions heated at 41 degrees C. We concluded that the use of thermosensitive liposomes and hyperthermia not only contributes to the brain tumour killing as direct thermal killing does but also helps to increase the concentration of chemotherapeutic drugs into the tumour invaded zones with mild local hyperthermia of 41 degrees C.
我们研究了使用热敏脂质体和热疗将药物递送至大脑的可能性。热敏脂质体是含有某些药物的小囊泡，其设计目的是在热疗作用下释放药物。第一个实验包括四组：（1）接受游离顺铂：顺二氨二氯铂（CDDP）；（2）接受游离CDDP并在41摄氏度以上进行局部脑部加热30分钟；（3）接受含CDDP的脂质体（CDDP-脂质体）；（4）接受CDDP-脂质体并在41摄氏度以上进行局部脑部加热30分钟。第（4）组的脑CDDP水平显著更高，而其他组则检测不到。在第二个实验中，我们研究了伊文思蓝（Eb）在杂种犬脑部人工加热区域的分布。一组接受游离Eb，另一组接受含Eb的脂质体（Eb-脂质体）。游离Eb的外渗局限于加热温度>44摄氏度的区域，而Eb-脂质体的外渗则扩展至加热温度为41摄氏度的区域。我们得出结论，使用热敏脂质体和热疗不仅像直接热杀伤那样有助于杀死脑肿瘤，而且有助于在41摄氏度的轻度局部热疗作用下增加化疗药物在肿瘤侵袭区域的浓度。
