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.

我们已经产生了杂化脂质体（HL），可以通过缓冲溶液中的水泡和胶束分子超声处理。 HL的物理特性，例如大小，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。我们已经采用了HL进行癌症研究，有趣的结果如下：（a）HL的均匀，稳定结构由Dimyristoistoyl磷脂酰胆碱（DMPC）组成（DMPC）和多氧乙烯（23）-Dodecyl-Ether（C12（E0）2）与80 nm的散射（c12（e0）2）均显示了80 nm的散布。达到了HL对人类B-淋巴瘤（Raji）细胞生长的显着抑制作用。使用流式细胞仪，DNA琼脂糖凝胶电泳，带有TUNEL方法和时束视频的显微照片可获得HL诱导凋亡。（c）使用HL治疗后，使用任何药物的癌变均进行了均衡，使用了均无作用的体重（D）（e）在临床应用中，在淋巴瘤的患者中，在静脉注射HL无副作用并显着降低了肿瘤后，在淋巴瘤的患者中长期生存，在局部局部给予混合脂质体后获得了近代的造成较大的免疫性细胞。（g）使用HL检查了庆大霉素治疗对杜钦肌营养不良的一种新型方法。用庆大霉素封装的HL处理的MDX小鼠未显示毒性，并且在注射源泉蛋白包裹的HL的MDX小鼠中肌营养不良蛋白阳性纤维的效率得到了效率。