Chemotherapy with hybrid liposomes and application to drug delivery system with hybrid liposomes

混合脂质体化疗及其在混合脂质体给药系统中的应用

基本信息

批准号：
17360403
负责人：
UEOKA Ryuichi
金额：
$ 10.48万
依托单位：
Sojo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

项目摘要

We have produced hybrid liposomes (HL) which can be prepared by sonication of vesicular and micellar molecules in a buffer solution. The physical properties of HL such as size, shape, membrane fluidity, and the temperature of phase separation can be controlled by changing the constituents and compositional ratio. We have employed HL for the research of cancers and interesting results are as follows;(A) The uniform and stable structure of HL composed of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene (23)-dodecyl ether (C12 (E0) 2) with a diameter of 80 nm was revealed on the basis of electron microscopy and dynamic light scattering measurements.(B) The remarkable inhibitory effects of HL on the growth of human-B-lymphoma (RAJI) cells were attained. Induction of apoptosis by HL was obtained using flow cytometry, DNA agarose gel electrophoresis, micrograph with TUNEL method and time-laps video.(C) Significantly prolonged survival and remarkable reduction of tumor volume were obtained using mice model of carcinoma after the treatment with HL without any drug.(D) There were no abnormal findings on blood test, hemato chemistry, relative organ weight and autopsy of normal rats after administering HL on the basis of chronic toxicity tests.(E) In clinical applications, prolonged survival was attained in patients with lymphoma after the intravenous injection of HL without any side effect and remarkable reduction of neoplasm was obtained after the local administration of hybrid liposomes.(F) Remarkable immunostimulation effects of HL on human peripheral blood mononuclear cells were obtained in vitro.(G) A novel approach of gentamicin therapy for Duchenne Muscular Dystrophy using HL was examined. Mdx mice treated with gentamicin encapsulated HL did not show toxicity and the efficiency of dystrophin positive fibers in the mdx mice injected with gentamicin encapsulated HL was obtained.

我们生产了混合脂质体 (HL)，它可以通过在缓冲溶液中超声处理囊泡和胶束分子来制备。 HL的物理性质，如尺寸、形状、膜流动性和相分离温度，可以通过改变成分和组成比来控制。我们将HL用于癌症的研究，有趣的结果如下：（A）由二肉豆蔻酰磷脂酰胆碱（DMPC）和聚氧乙烯（23）-十二烷基醚（C12（E0）2）组成的HL均匀稳定的结构，直径在电子显微镜和动态光散射测量的基础上揭示了80 nm的特征。(B) HL对人B淋巴瘤生长的显着抑制作用(RAJI)细胞被获得。通过流式细胞术、DNA琼脂糖凝胶电泳、TUNEL法显微照片和延时视频获得HL诱导细胞凋亡的结果。(C) HL治疗后，癌症小鼠模型的生存期显着延长，肿瘤体积显着减小。 (D)根据慢性毒性试验，给予正常大鼠HL后，血液检查、血液化学、相对器官重量和尸检均未发现异常。(E)在临床应用中，长期静脉注射HL后，淋巴瘤患者获得了存活，且无任何副作用；局部给予混合脂质体后，肿瘤明显减少。（F）体外获得HL对人外周血单个核细胞的显着免疫刺激作用(G) 研究了一种使用 HL 庆大霉素治疗杜氏肌营养不良症的新方法。用庆大霉素封装的HL治疗的Mdx小鼠没有表现出毒性，并且获得了注射庆大霉素封装的HL的mdx小鼠中抗肌营养不良蛋白阳性纤维的效率。