磁性体・抗がん剤同時封入温度感受性血中滞留型リポソームを用いた温熱化学療法の開発

使用封装磁性材料的温度敏感血液保留脂质体和抗癌药物开发热化疗

• 批准号: 17659454
• 负责人: 継 淳
• 金额: $ 2.11万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Exploratory Research
• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17659454/
• 关键词: 温度感受性ステルスリポソーム; 脳腫瘍; 温熱化学療法; ドキソルビシン; 温熱療法; ステルスリポソーム

昨年度は温度感受性ステールスリポソームにDoxorubicin(DXR)封入をしたもの(DXR-TSL)を作成しまずはin vitroにおける薬物動態をした。封入されたDXRは、37℃の生理食塩水や37℃のラット血漿中ではほとんど放出されず、相転移温度である45℃の血漿中でのみ速やかに放出されることを確認した。さらにこのDXR-TSLをin vivoの系で体内薬物動態をしたところ、1)細網内皮への取り込みが回避されすぐれた血滞留性をもつこと 2)腫瘍局所を加温することで腫瘍組織内DXR量が非加温群より30倍集積する、という期待通りの薬物動態を示すことを確認した。本年度は昨年度に引き続きこのDXR-TSLによる抗腫瘍効果を複数の実験系により詳細に検討した。ヒト大腸がんヌードマウス皮下移植株をもちいて、(1)DXR-TSLを全身投与し直後から腫瘍局所を加温群 (2)DXR-TSLを投与するが加温しない群 (3)DXR単独投与群 (4)薬剤投与せず局所加温のみ行なう群 (5)コントロール群にわけそれぞれ治療効果を判定すべく3週間の腫瘍増殖曲線を比較した。また治療の副作用として体重減少についても計測した。するとDXR-TSLを投与し局所加温を加えた群がもっとも強い腫瘍増殖抑制効果を示すことがわかった。しかもこの群では体重減少も最も少なかった。この結果は再現性をもって証明された。ざらにこのDXL-TSLにMRI造影剤であるガドリニウムをも時封入させたリポソームを調整してみたが、した処方は残念ながらできなかった。すなわち、相転移温度まで腫瘍局所を加温することで移植された腫瘍のガドリニウムによる造影効果は残念ながら確認できなかった。

Doxorubicin (DXR) is a temperature-sensitive substance that can be encapsulated in a solvent (DXR-TSL). Encapsulated DXR, physiological water at 37 ℃, plasma at 37 ℃, phase shift temperature at 45 ℃, plasma at 37 ℃, phase shift temperature at 37 ℃, phase shift temperature at 45 ℃, phase shift temperature at 37 ℃, phase shift temperature at 37 ℃, phase shift temperature at 45 ℃, phase shift temperature at 37 ℃, phase shift temperature at 45 ℃, phase shift temperature at 45 ℃, phase shift temperature at 37 ℃, phase shift temperature at 45 ℃, phase shift temperature at 45 ℃, phase shift temperature at 37 ℃, phase shift temperature at 45 ℃, phase shift temperature at 45 ℃, The DXR-TSL in vivo system is characterized by the following: (1) the amount of DXR in tumor tissue is 30 times higher than that in non-heated group;(2) the amount of DXR in tumor tissue is 30 times higher than that in non-heated group;(3) the amount of DXR in tumor tissue is 30 times higher than that in non-heated group; and (4) the amount of DXR in vivo system is characterized by the following: (1) the amount of DXR-TSL in tumor tissue is 30 times higher than that in heated group. This year's DXR-TSL anti-tumor effect is discussed in detail. (1) DXR-TSL was administered to the whole body, and then the tumor cells were warmed up;(2) DXR-TSL was administered to the whole body, and then the tumor cells were warmed up;(3) DXR was administered alone and alone;(4) DXR-TSL was administered to the whole body, and then the tumor cells were warmed up;(5) DXR-TSL was administered to the whole body, and then the tumor cells were warmed up;(6) DXR-TSL was administered to the whole body, and then the tumor cells were warmed up;(7) DXR-TSL was administered to the whole body, and then the tumor cells were warmed up;(8) DXR-TSL was administered alone and alone;(9) DXR-TSL was administered to the whole body, and then the tumor cells were warmed up;(9) DXR-TSL was administered to the whole body, and then the tumor cells were warmed up;(9) DXR-TSL was administered to the whole body, and then the tumor cells were warmed up;(9) DXR-TSL was Side effects of treatment are measured in weight loss. DXR-TSL is the most effective way to increase productivity. The weight loss is the least. The results were reproducible and proved to be accurate. Dxl-tsl MRI imaging system The temperature of the tumor was changed from zero to zero. The tumor was transplanted and the imaging results confirmed.