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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.

我们制备了一种杂化脂质体（HL），它可以通过在缓冲溶液中对囊泡和胶束分子进行超声处理来制备。通过改变HL的组分和组成比，可以控制HL的尺寸、形状、膜流动性和相分离温度等物理性质。我们使用HL进行癌症研究，有趣的结果如下：(A)通过电子显微镜和动态光散射测量，揭示了二myristoylphosphatidycholine （DMPC）和聚氧乙烯(23)-十二烷基醚（C12 (E0) 2）组成的直径为80 nm的HL均匀稳定的结构。(B) HL对人B淋巴瘤（RAJI）细胞的生长有明显的抑制作用。采用流式细胞术、DNA琼脂糖凝胶电泳、TUNEL显微摄影和延时视频观察HL对细胞凋亡的诱导作用。(C)在不使用任何药物的情况下，用HL治疗小鼠肿瘤模型后，存活时间明显延长，肿瘤体积明显减小。(D)在慢性毒性试验的基础上，给药后正常大鼠的血液检查、血液化学、相对脏器重量和尸检均未见异常。(E)在临床应用中，淋巴瘤患者静脉注射HL后可延长生存期，无任何副作用，局部给药混合脂质体后可显著减少肿瘤。(F) HL对体外培养的人外周血单个核细胞有明显的免疫刺激作用。(G)研究了一种庆大霉素治疗杜氏肌营养不良的新方法。庆大霉素包封HL对Mdx小鼠无毒性作用，并观察了庆大霉素包封HL对Mdx小鼠肌营养不良蛋白阳性纤维的影响。