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

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 16591480
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kanazawa University
• Principal Investigator: TSUCHIYA Hiroyuki Kanazawa University, Graduate School of Medicine, Associate Professor (40227434)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Norio Kanazawa University, Graduate School of Medicine, Assistant (90332668)
• Project Period (FY): 2004 – 2006
• Keywords: Osteosarcoma / Pegylated liposome / Cisplatin / Caffeine

Research Abstract

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 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.