Intrathecal chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea encapsulated into hybrid liposomes for meningeal gliomatosis: an experimental study.
Intrathecal chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea encapsulated into hybrid liposomes for meningeal gliomatosis: an experimental study.
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将 1,3-双（2-氯乙基）-1-亚硝基脲封装到混合脂质体中进行鞘内化疗治疗脑膜胶质瘤病：一项实验研究。
作者：
I. Kitamura;M. Kochi;Y. Matsumoto;R. Ueoka;J. Kuratsu;Y. Ushio
1，3-双（2-氯乙基）-1-亚硝基脲（BCNU）是氯乙基亚硝基脲类化合物之一，对恶性胶质瘤有较好的治疗作用。为了开发其在鞘内化疗中的用途，我们将BCNU封装在由二肉豆蔻酰磷脂酰胆碱和胶束表面活性剂（吐温20）组成的混合脂质体中，并将其溶解在人工脑脊液（lipo-BCNU）中。然后，我们研究了混合脂质体的毒性和lipo-BCNU在体外的细胞增殖抑制。我们发现，3 mM的混合脂质体不影响人内皮细胞的生存能力和lipo-BCNU抑制人胶质瘤细胞系U-105 MG，U-251 MG，和U-373 MG，和大鼠胶质瘤细胞系C6和9 L的增殖在浓度依赖性的方式。脑池内注射lipo-BCNU的Wistar大鼠没有表现出体重减轻、神经系统症状或大脑和脊髓的组织学变化。通过脑池内接种0.1 ml含有1 × 10（6）或5 × 10（6）个活C6胶质瘤细胞的细胞悬液建立脑膜胶质瘤病Wistar大鼠模型。接种后2天，脑池内给予lipo-BCNU（BCNU，2.5 mg/kg）。当接种1 × 106个胶质瘤细胞时（实验1和2），对照组的中位存活时间为24.5和26天，而脂质体-BCNU治疗组的中位存活时间为32和45天。分别当接种5 × 10（6）个胶质瘤细胞时（实验3-6），对照组中的中位存活时间为17-29.5天，处理组中的中位存活时间为23-44天。在六个实验组中的三个中获得了显著延长的生存期。将1 ml lipo-BCNU（BCNU，4.67 mM）或1 ml用5%葡萄糖/水溶解的BCNU（BCNU，4.67 mM）注入犬小脑延髓池后，采集小脑延髓池脑脊液，并通过高效液相色谱法测定BCNU浓度。脂质体BCNU的半衰期比用5%葡萄糖/水溶解的BCNU的半衰期长。这些结果表明，鞘内注射lipo-BCNU治疗脑膜胶质瘤病是可能的。
1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), one of the chloroethyl nitrosoureas, is effective against malignant glioma. To develop its use in intrathecal chemotherapy, we encapsulated BCNU in hybrid liposomes composed of dimyristoylphosphatidylcholine and micellar surfactants (Tween 20) and dissolved it in artificial cerebrospinal fluid (lipo-BCNU). We then studied the toxicity of hybrid liposomes and cellular proliferation inhibition of lipo-BCNU in vitro. We found that 3 mM hybrid liposomes did not affect the viability of human endothelial cells and that lipo-BCNU inhibited the proliferation of human glioma cell lines U-105MG, U-251MG, and U-373MG, and rat glioma cell lines C6 and 9L in a concentration-dependent fashion. Wistar rats that were administered lipo-BCNU intracisternally showed no weight loss, neurological symptoms, or histological changes of the brain and spinal cord. A Wistar rat model of meningeal gliomatosis was established by intracisternal inoculation of 0.1 ml cell suspension containing 1 x 10(6) or 5 x 10(6) viable C6 glioma cells. Two days after inoculation, lipo-BCNU (BCNU, 2.5 mg/kg) was administered intracisternally. When 1 x 10(6) glioma cells were inoculated (experiments 1 and 2), the median survival times were 24.5 and 26 days in the control groups and 32 and 45 days in the lipo-BCNU-treated groups. respectively. When 5 x 10(6) glioma cells were inoculated (experiments 3-6), the median survival times were 17-29.5 days in the control groups and 23-44 days in the treated groups, respectively. Significantly prolonged survival was obtained in three of six experimental groups. After the administration of 1 ml lipo-BCNU (BCNU, 4.67 mM) or 1 ml BCNU solubilized with 5% dextrose/water (BCNU, 4.67 mM) into the cisterna magna of dogs, the cisterna magna cerebrospinal fluid was sampled, and the BCNU concentrations were assayed by high-performance liquid chromatography. The half-life of the lipo-BCNU was longer than that of BCNU solubilized with 5% dextrose/water. These results suggest that the intrathecal administration of lipo-BCNU may be possible for the treatment of meningeal gliomatosis.
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含有 1-β-D-阿拉伯呋喃糖基胞嘧啶的多囊脂质体，用于缓释鞘内治疗。
影响因子：
11.2
作者：
Kim,S;Kim,DJ;Geyer,MA;Howell,SB
通讯作者：
Howell,SB
影响因子：
11.2
作者：
S. Kim;S. Khatibi;Stephen B. Howell;C. McCully;F. Balis;D. Poplack
通讯作者：
S. Kim;S. Khatibi;Stephen B. Howell;C. McCully;F. Balis;D. Poplack
比格犬脑室内3-[(4-氨基-2-甲基-5-嘧啶基)乙基]-1-(2-氯乙基)-1-硝基脲和其他亚硝基脲的中枢神经系统毒性和脑脊液药代动力学。
影响因子：
11.2
作者：
Levin,VA;Byrd,D;Campbell,J;Giannini,DD;Borcich,JK;Davis,RL
通讯作者：
Davis,RL
DOI：
10.1159/000120013
发表时间：
1981
期刊：
Child's brain
影响因子：
--
作者：
Edwards,MS;Levin,VA;Seager,ML;Wilson,CB
通讯作者：
Wilson,CB