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Study of liposomes as drug-carrier.

脂质体作为药物载体的研究。

基本信息

批准号：
58870066
负责人：
SAITO Kazuhisa
金额：
$ 3.01万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1983
资助国家：
日本
起止时间：
1983 至 1985
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-58870066/
关键词：
drug-carrier liposome hepatoma salmonellosis diabetes missile therapy アドリアマイシン経口インスリン

项目摘要

1. Liposome-entrapped streptomycin(L-SM) was very effective against salmonellosis in mice, although free SM was ineffective. Entrapment in liposomes markedly reduced the acute toxicity of SM. Large amounts of SM accumulated in the liver and spleen after i.v. injection of L-SM, and growth of salmonella in these organs was effectively inhibited.2. Adriamycin(Ad) entrapped in anti-human <alpha> -fetoprotein(AFP) monoclonal antibody-conjugated liposomes bound selectively to AFP-producing human hepatoma cells and inhibited their growth in vitro, and also inhibited the growth of the human hepatoma implanted under the skin or the capsule of the liver of nude mice as assessed from the tumor-weight and blood concentraion of AFP. Entrappment in liposomes reduced the toxicity of Ad.3. Intragastric administration of liposome-entrapped insulin reduced blood sugar in only one out of four streptozotocin-induced diabetic mice, and no relation was observed between the decrease of blood sugar and blood concentration of insulin. Intraperitoneal injection of liposome-entrapped insulin reduced blood sugar in four out of six diabetic mice, and in this case the decrease of blood sugar coincided with blood concentration of insulin. These results indicate that improvement in the preparation of liposomes should be necessary to achieve successfull oral administration of insulin for therapy of diabetes mellitus.

1.脂质体包裹的链霉素(L-SM)对小鼠沙门氏菌病有很好的治疗作用，而游离SM则无效。脂质体的包封率明显降低SM的急性毒性。静脉注射后，丹参在肝、脾中大量蓄积。结论：1.注射L-SM可有效抑制沙门氏菌在上述脏器的生长。抗人甲胎蛋白(AFP)单抗偶联脂质体包裹的阿霉素(Ad)能选择性地与产生AFP的人肝癌细胞结合并在体外抑制其生长，从AFP的瘤重和血药浓度来看，也能抑制裸鼠皮下或肝被膜下人肝癌的生长。脂质体的包埋降低了Ad.3的毒性。4只链脲佐菌素诱导的糖尿病小鼠中只有1只被脂质体包裹的胰岛素灌胃后血糖下降，而血糖的降低与胰岛素的血药浓度之间没有关系。在6只糖尿病小鼠中，有4只通过腹腔注射脂质体包裹的胰岛素降低了血糖，在这种情况下，血糖的降低与胰岛素的血药浓度一致。这些结果表明，为了成功地口服胰岛素治疗糖尿病，需要改进脂质体的制备方法。