DEVELOPMENT OF FUNCTIONAL RES-AVOIDING LIPOSOMES AND THEIR USE IN CANCER THERAPY

功能性再避免脂质体的开发及其在癌症治疗中的应用

• 批准号: 05671874
• 负责人: OKU Naoto
• 金额: $ 1.41万
• 依托单位: UNIVERSITY OF SHIZUOKA
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671874/
• 关键词: liposomes; reticuloendothelial system; drug delivery system; cancer therapy; long-curculating liposomes; RES回避; 温度感受性; 抗腫瘍

Liposomes have been used as drug carriers in the field of drug delivery system (DDS).In this research, we focused on the effective targeting of liposomes and effective release of liposomal contents at the target site.At first, we developed thermosensitive liposomes which could release macromolecules encapsulated.Thermosensitive liposomes have been developed using saturated phospholipids of which phase transition temperature is slightly hygher than body temperature. We succeeded macromolecule release from these liposomes by the increase of internal osmotic pressure.Secondly, we applied RES-avoiding liposomes which had been developed by ourselves on the cancer therapy.RES-avoiding liposomes are known to be accumulated in tumor tissued by passive targeting, since they tend to reside in bloodstream and to leak out into tumor tissues through leaky endothelium.In fact, adriamycin-encapsulated RES-avoiding liposomes caused suppression of tumor volume, reduction of side effect, and prolonging of survial time in tumor-bearing mice.Multi-dose administration of the liposomes caused 40% curing of the animal.We also developed a hydrophobic anticancer prodrug, which is ready to be incorporated in liposomes, and observed the therapeutic effect of the drug.Our results progress the practical usage of functional liposomes in DDS field.

脂质体作为药物载体已广泛应用于药物传递系统（DDS）领域，本研究围绕脂质体的有效靶向性和脂质体内容物在靶位的有效释放展开，首先研制了能够释放大分子的温敏脂质体，利用相变温度略高于体温的饱和磷脂制备了温敏脂质体，并对温敏脂质体的结构进行了研究。我们成功地通过增加内渗透压从这些脂质体中释放大分子。其次，我们将我们自己开发的RES-避免脂质体应用于癌症治疗。已知RES-避免脂质体通过被动靶向在肿瘤组织中积聚，因为它们倾向于驻留在血流中并通过渗漏的内皮渗漏到肿瘤组织中。事实上，阿霉素缓释脂质体能有效抑制荷瘤小鼠的肿瘤体积，减少毒副作用，延长荷瘤小鼠的生存时间，多次给药治愈率达40%。本研究结果为功能性脂质体在DDS领域的实际应用提供了新的思路。

项目成果

N.OKU: "Therapeutic Effect of Adviamycin Encapsulated in Long-ciralating Liposames on Meth-A-bearing Mice" Int.J.Cancer. 58. 415-419 (1994)

N.OKU：“长循环脂质体中包裹的阿维亚霉素对携带 Meth-A 的小鼠的治疗效果”Int.J.Cancer。

Y.Namba: "Liposomal Applications to Cancer Therapy" J.Bioactive and Compatible Polymers. 8. 158-177 (1993)

Y.Namba：“脂质体在癌症治疗中的应用”J.生物活性和相容聚合物。

N.OKU: "Therapeutic Efficacy of 5-fluoromacil Prodrugs Using Endogenous Serum Prateins as Drug Carriersi A New Strategy in Drug Delivey System" Biol.Pharm.Bull.18. 181-184 (1995)

N.OKU：“使用内源性血清蛋白作为药物载体的 5-氟马西尔前药的治疗效果——药物输送系统的新策略”Biol.Pharm.Bull.18。

N.OKU: "Potential Usage of Thermosensitive Liposomes for Macromolecule Delivery" Biochim.Biophys.Acta. 1191. 389-391 (1994)

N.OKU：“热敏脂质体在大分子递送中的潜在用途”Biochim.Biophys.Acta。

K.Doi: "Therapeutic Effect of RES-avoiding liposomes Containing a phospholipid analogue of 5FU in Meth A Sorcoma-bearing Mice" Biol.Pharm.Bull.17. 1414-1416 (1994)

K.Doi：“含有 5FU 磷脂类似物的 RES 避免脂质体对携带 Meth A 肉瘤的小鼠的治疗效果”Biol.Pharm.Bull.17。