Cationized catalase-loaded hydrogel for growth inhibition of peritoneally disseminated tumor cells.
A previous study demonstrated that ethylenediamine-conjugated catalase (ED-catalase) inhibits peritoneal dissemination of tumor cells in mice. To increase its inhibitory effects by sustained release, a hydrogel formulation of ED-catalase was prepared using a biodegradable hydrogel consisting of an acidic gelatin with an isoelectric point of 5.0. Although intraperitoneally injected ED-catalase solution rapidly disappeared from the cavity, more than 10% of ED-catalase remained even at 14 days after implantation of ED-catalase/hydrogel into the cavity. Then, the effect of ED-catalase/hydrogel on peritoneal dissemination of tumor cells was evaluated by measuring the luciferase activity of abdominal organs after intraperitoneal inoculation of colon26/Luc, a colon adenocarcinoma stably expressing luciferase. ED-catalase/hydrogel showed a significantly (P<0.05) greater effect on inhibiting the growth of tumor cells than ED-catalase solution, demonstrating the importance of the retention of ED-catalase within the cavity as far as inhibition is concerned. Serial in vivo images of luciferase activity revealed that the ED-catalase/hydrogel significantly (P<0.05) retarded the growth rate of tumor cells. Survival of tumor-bearing mice supported the findings obtained with the luminescence-based analyses. These findings indicate that the sustained release of ED-catalase from hydrogels into the cavity is highly effective in inhibiting the growth of peritoneally disseminated tumor cells.
Hyoudou
Kenji
K
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Nishikawa
Makiya
M
Ikemura
Mai
M
Kobayashi
Yuki
Y
Mendelsohn
Adam
A
Miyazaki
Nobuhiko
N
Tabata
Yasuhiko
Y
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000230:Adenocarcinoma / Q000517:prevention & control* / Q000556:secondary; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D002374:Catalase / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D002412:Cations; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D005029:Ethylenediamines / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry*; D017930:Genes, Reporter; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D008156:Luciferases; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010534:Peritoneal Neoplasms / Q000517:prevention & control* / Q000556:secondary; D012995:Solubility; D014018:Tissue Distribution; D014162:Transfection
D000970:Antineoplastic Agents; D002412:Cations; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005029:Ethylenediamines; D020100:Hydrogels; C031234:ethylenediamine; D005780:Gelatin; D002374:Catalase; D008156:Luciferases