Research of the chemotherapy for osteosarcoma with the liposome with amphipathic polyethylene glycol(PEG) encapsulating anticancer agent or caffeine.

两亲性聚乙二醇(PEG)包裹抗癌剂或咖啡因的脂质体治疗骨肉瘤化疗的研究。

• 批准号: 16591480
• 负责人: TSUCHIYA Hiroyuki
• 金额: $ 2.18万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591480/
• 关键词: Osteosarcoma; Pegylated liposome; Cisplatin; Caffeine; シスプラチン封入リポゾーム; カフェイン封入リポゾーム

We prepared the liposome with amphipathic polyethylene glycol (PEG) encapsulating caffeine (CAF-L). At first we administered CAF-L to rat via vein, and it was proved that CAF-L had a property of prolonged circulation in rat. But the quantity of caffeine encapsulated in liposome was is not high enough for us to assess the clinical effect of CAF-L.To assess the accumulation of liposome in osteosarcoma, we prepared the liposome encapsulating the fluorescent material (fluoresceine). The character of this liposome is that fluoresceine can emit light only that the liposome is ruptured. We administered this liposome to a rat transplanted solid osteosarcoma subcutaneously. The specimen from the tumor excised in 24 hours after injection via vein of the liposome emitted light enough under a microscope. From this result we concluded the liposome had a property accumulating to a solid osteosarcoma, we prepared the liposome encapsulating cisplatin (CDDP-L) by the same method. We investigated experi … More mentally in vivo the movement, the antitumor effect and the effect by administration with caffeine. Firstly we administered liquid cisplatin or CDDP-L to rats, and it was become clear that CDDP-L was prolonged circulating. Secondly we administered liquid cisplatin or CDDP-L to the rats subcutaneously transplanted solid osteosarcoma and measured the concentration of platinum in the tumor. The concentration of platinum in the tumor at 12 hours after injection of CDDP-L was almost equal to that after injection of liquid cisplatin, but the concentration at 24 hours after injection of CDDP-L was significantly superior to that after injection of liquid cisplatin. Then we examined the antitumor effect of CDDP-L in vivo. The tumor size at 14 days after venous injection of CDDP-L in dose of 1.75 mg/kg was not different from after injection of liquid cisplatin in the same dose. And we investigated the antitumor effect by administration of CDDP-L with caffeine. We set up the four groups; a group (I) administered one shot liquid cisplatin and the following injected of caffeine in three days, a group (II) one shot liquid cisplatin and the following caffeine in seven days, a group (III) one shot CDDP-L and the following caffeine in three days, a group (VI) one shot CDDP-L and the following caffeine in seven days. In the four group, at the group VI the antitumor effect was superior significantly than the other groups statistically. From this result we concluded that CDDP-L was continuously releasing cisplatin to a solid tumor for a long time and the a long spell of administration of the following caffeine enhanced the antitumor effect of CDDP-L. Less

以两亲性聚乙二醇（PEG）包封咖啡因（cafl）制备脂质体。首先通过大鼠静脉给药，证明了cafl在大鼠体内具有延长循环的特性。但脂质体中咖啡因的包封量尚不足以评价其临床效果。为了评估脂质体在骨肉瘤中的积累，我们制备了包封荧光材料（荧光素）的脂质体。这种脂质体的特点是荧光素只有在脂质体破裂时才能发光。我们将这种脂质体用于大鼠移植的实体骨肉瘤皮下注射。经静脉注射脂质体后24小时切除的肿瘤标本在显微镜下发出足够的光。由此得出脂质体具有形成实体骨肉瘤的特性，我们用同样的方法制备了顺铂包封脂质体（CDDP-L）。实验研究了脑内运动、抗肿瘤作用和咖啡因给药的作用。首先给予大鼠液体顺铂或CDDP-L， CDDP-L明显延长循环。其次，我们给大鼠皮下移植的实体骨肉瘤注射液体顺铂或CDDP-L，并测量肿瘤中铂的浓度。注射CDDP-L后12小时肿瘤内铂浓度与注射顺铂液后铂浓度基本相等，但注射CDDP-L后24小时铂浓度明显优于注射顺铂液后铂浓度。然后在体内检测CDDP-L的抗肿瘤作用。静脉注射1.75 mg/kg剂量的CDDP-L后14 d的肿瘤大小与注射相同剂量的液体顺铂后14 d的肿瘤大小无差异。并观察CDDP-L与咖啡因联合给药的抗肿瘤作用。我们设立了四个小组；一组(I)连续3天注射1针液体顺铂并随后注射咖啡因，一组（II）连续7天注射1针液体顺铂并随后注射咖啡因，一组（III）连续3天注射1针CDDP-L并随后注射咖啡因，一组（VI）连续7天注射1针CDDP-L并随后注射咖啡因。在四组中，第六组的抗肿瘤效果明显优于其他组，具有统计学意义。由此我们得出结论，CDDP-L在实体瘤中持续释放顺铂的时间较长，后续长期给药咖啡因可增强CDDP-L的抗肿瘤作用。少