TY - JOUR
T1 - Efficacy of lactosaminated and intact N-succinyl-chitosan-mitomycin C conjugates against M5076 liver metastatic cancer
AU - Kato, Yoshinori
AU - Onishi, Hiraku
AU - Machida, Yoshiharu
PY - 2002
Y1 - 2002
N2 - In this study, lactosaminated N-succinyl-chitosan (Lac-Suc) was investigated for its liver targeting ability in the early metastatic stage of liver cancer, and subsequently Lac-Suc-mitomycin C conjugate (Lac-Suc-MMC) and highly-succinylated N-succinyl-chitosan (Suc(II))-MMC conjugate (Suc(II)-MMC) were examined for efficacy against the liver metastasis. Mice into which M5076 cells were inoculated intravenously were used as liver metastatic models. Fluorescently labelled Lac-Suc (Lac-Suc-FTC) was intravenously administered at a daily dose of 0.2 mg/mouse for 4 days or at a single dose of 0.8 mg/mouse at 3 days post-inoculation. At a dose of 0.2 mg/mouse for 4 days, liver accumulation of Lac-Suc-FTC was increased after all except the fourth injection, indicating that the capacity of accumulation might be limited to around 110 μg per mouse with repeated daily administration at 0.2 mg/mouse. As to the efficacy of intravenous administration at 7 days post-inoculation, Lac-Suc-MMC was less effective at a dose of 1 mg kg-1 for 4 days than a single dose of 4 mg kg-1. This result was not in accordance with that expected from the biodistribution study. On the other hand, with intravenous administration at 3 days post-inoculation, Suc(II)-MMC was more effective on repeated administration, and it showed higher efficacy than Lac-Suc-MMC at both 1 mg kg-1 for 4 days and 4 mg kg-1 as a single dose. Further, with intravenous administration at 3 days post-inoculation, Suc(II)-MMC exhibited a much higher survival effect at a dose of 4 mg kg-1 for 4 days.
AB - In this study, lactosaminated N-succinyl-chitosan (Lac-Suc) was investigated for its liver targeting ability in the early metastatic stage of liver cancer, and subsequently Lac-Suc-mitomycin C conjugate (Lac-Suc-MMC) and highly-succinylated N-succinyl-chitosan (Suc(II))-MMC conjugate (Suc(II)-MMC) were examined for efficacy against the liver metastasis. Mice into which M5076 cells were inoculated intravenously were used as liver metastatic models. Fluorescently labelled Lac-Suc (Lac-Suc-FTC) was intravenously administered at a daily dose of 0.2 mg/mouse for 4 days or at a single dose of 0.8 mg/mouse at 3 days post-inoculation. At a dose of 0.2 mg/mouse for 4 days, liver accumulation of Lac-Suc-FTC was increased after all except the fourth injection, indicating that the capacity of accumulation might be limited to around 110 μg per mouse with repeated daily administration at 0.2 mg/mouse. As to the efficacy of intravenous administration at 7 days post-inoculation, Lac-Suc-MMC was less effective at a dose of 1 mg kg-1 for 4 days than a single dose of 4 mg kg-1. This result was not in accordance with that expected from the biodistribution study. On the other hand, with intravenous administration at 3 days post-inoculation, Suc(II)-MMC was more effective on repeated administration, and it showed higher efficacy than Lac-Suc-MMC at both 1 mg kg-1 for 4 days and 4 mg kg-1 as a single dose. Further, with intravenous administration at 3 days post-inoculation, Suc(II)-MMC exhibited a much higher survival effect at a dose of 4 mg kg-1 for 4 days.
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U2 - 10.1211/0022357021778646
DO - 10.1211/0022357021778646
M3 - Article
C2 - 11999131
AN - SCOPUS:0036230313
SN - 0022-3573
VL - 54
SP - 529
EP - 537
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
IS - 4
ER -