Project/Area Number |
02670582
|
Research Category |
Grant-in-Aid for General Scientific Research (C)
|
Allocation Type | Single-year Grants |
Research Field |
Digestive surgery
|
Research Institution | Nagasaki University |
Principal Investigator |
SEGAWA Tohru Second Department of Surgery, Nagasaki University School of Medicine, Assistant Professor, 医学部, 講師 (40196936)
|
Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Masayuki Second Department of Surgery, Nagasaki University School of Medicine, Resident, 医学部, 医員
IZAWA Kunihide Second Department of Surgery, Nagasaki University School of Medicine, Associate, 医学部, 助教授 (40124820)
|
Project Period (FY) |
1990 – 1991
|
Project Status |
Completed (Fiscal Year 1991)
|
Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1991: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1990: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
Keywords | Pullulan / Active Targeting / l-Amino-Lacotose / Polysaccharide Coated Liposomes / AH66 / HuH7 / Hepatocyte / Adriamycin / プルヲン / lーアミノーラクト-ス / 腹腔マクロファ-ジ / 粒子径 / pullulan / ^<14>C標識リポソ-ム / galactosamine / lactose / コラゲナ-ゼ潅流法 / ^3H標識イヌリン |
Research Abstract |
Although normal liver parenchymal cells have galactose-specific asialoglycoprotein receptors, little is known about the other regulatory factors except for terminal non-reduced galactose. The in-vitro uptakes of liposomes coated with polysaccharide into a rat hepatoma cell line (AH66 cells), human hepatoma cell line (HuH7) and isolated rat liver parenchymal cells (hepatocytes) were investigated. Two polysaccharides were employed in the experiments : cholesterol Pullulan (CHP) (control) and 1-amino-lactose CHP (lac-CHP) bearing a molecular recognition site. CHP-coated liposomes were used as control because conventional liposomes were less stable than polysaccharides (such as CHP)-coated liposomes. The uptakes of lac-CHP into AH66 and HuH7 cells were about 2.9 and 4.4 times those of CHP for 3 hours, respectively. The uptake of these substances into hepatocytes was almost the same as that of CHP. The antitumor effect of adriamycin entrapped in two types of liposomes was tested and demonstrated that lac-CHP coated liposomes were more effective than CHP-coated liposomes. The in-vivo uptake of lac-CHP into AH66 cells growing in nudemice was higher than that of CHPcoated liposomes. We analyzed the size of liposomes and found better uptake into AH66 cells in 50 nm sized if these substances than 350 nm sized. Considering that polysaccharide-coated liposomes become more stable, both physiochemically and biochemically, than conventional liposomes, lac-CHP-coated liposomes may be very useful in targeting hepatoma cells.
|