Tumour cell uptake of lactosaminated and intact N-succinyl-chitosans and antitumour effects of conjugates with mitomycin C.
BACKGROUND
The relationship between the uptake of lactosaminated and intact N-succinyl-chitosans into hepatoma cells (MH134 and AH130) and liver metastatic tumour model cells (M5076) and the antitumour effects of their conjugates with mitomycin C (MMC) were investigated.


METHODS
Fluorescently-labelled carriers were administered to tumour-bearing mice. The fluorescence intensity and microscopic examinations were performed at 1 hour post-injection. The antitumour effects were examined according to several schedules: one of them was the administration of each conjugate at a dose of 4 mg eq. MMC/kg x 4 days at 3 days post-inoculation.


RESULTS
A difference in uptake was found by measurement of fluorescence intensity between both carriers only in MH134 cells, but was not recognized by fluorescence microscopy. Among these cell lines, the uptake of carriers into M5076 cells tended to be the most extensive. The difference in antitumour effects of the conjugates against MH134 and M5076 was reflected by the biodistribution study.


CONCLUSIONS
The pattern of antitumour effects was markedly different among cell lines of different origins.
Kato
Yoshinori
Y
Department of Drug Delivery Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. yk-no.1@jcom.home.ne.jp
Onishi
Hiraku
H
Machida
Yoshiharu
Y
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002686:Chitin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D048271:Chitosan; D004337:Drug Carriers / Q000493:pharmacokinetics; D005260:Female; D007785:Lactose / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000556:secondary; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016685:Mitomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; C118639:N-succinyl-chitosan; D002686:Chitin; D016685:Mitomycin; D048271:Chitosan; D007785:Lactose