| Project/Area Number |
63480310
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Keio University |
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Principal Investigator |
ISHIBIKI Kyuya Depart. of Surgery, Keio Univ. Assoc. Prof., 医学部・外科, 助教授 (10051236)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Hiroyuki Dept. of Surg., School of Med. Keio Assistant, Univ., 医学部・外科, 助手 (00206210)
UYAMA Ichro Dept. of Surg., School of Med. Keio Assistant, Univ., 医学部・外科, 助手 (60193950)
HIRAHATA Shinobu Dept. of Surg., School of Med. Keio Assistant, Univ., 医学部・外科, 助手 (40189858)
KUMAI Koichiro Dept. of Surg., School of Med. Keio Assistant, Univ., 医学部・外科, 助手 (30101984)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1990: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1989: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1988: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Keywords | Adriamycin Entrapped in Liposomes / Monoclonal Antibody / Fab Fragment / F(ab')_2 Fragment / Temperature-sensitive Liposomes / Reticuloendotherial System / Local Hyperthermia / CDDP Delivertive Entrapped in Liposomes / Fab′フラグメント / タ-ゲティング効果 / 網内系対策 / F(ab′)^2フラグメント化モノクロ-ナル抗体 / 抗CEAモノクロ-ナル抗体 / CDD系薬剤封入リポ-ム / Fabフラグメント化モノクローナル抗体 / F(ab')^2フラグメント / アドリアマイシン封入リポソーム / CDDP系薬剤入りリポソーム |
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| Research Abstract |
Liposomes are artificial phospholipid vesicles consisting of lipid bilayers. They can be used as drug-carriers for drug delivery system (DDS), by entrapped antitumor drugs in the vesicles. We conducted experimental studies of 2 types of DDS using adriamycin (ADM) entrapped in liposomes (Lip-ADM).
(1) Lip-ADM conjugated with tumor associated monoclonal antibpdies or their Fab or Fab' fragments showed the selective delivery of ADM and the targeted antitumor effect against sntigen-producing xenograft in vivo. Pepsin digestion of monoclonal antibodies produced Fab fragments from anti-AFP IgG2b antibodies and Fab' fragments from anti-CEA IgGl antibodies. Fab' fragments should be useful for DDS in cancer chemotherapy.
(2) Liposomes have the specific liguid-crystalline phase transition temperature (Tc), at which they release entrapped drugs. The temperature-sensitive liposomes encapsulating ADM (TS-Lip ADM) prepared from dipalmitoylphosphatidylcholine (Tc:41ﾟC) and cholesterol, showed the temperature-sensitive release of ADM and the enhanced antitumor effects by combination of local hyperthermia of the tumor AH66.
(3) CDDP and it's delivertive NK-121 were tried to be entrapped in liposomes.
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