Anti-tumor effect of intraperitoneal administration of cisplatin-loaded microspheres to human tumor xenografted nude mice.
This study evaluates the anti-tumor effect of cisplatin-loaded microspheres (CDDP-MS) against peritoneal carcinomatosis using human tumor xenografts. The incorporated CDDP was released from CDDP-MS for 3 weeks in vivo as well as in vitro. CDDP-MS at a dose of 35 mg/kg (at maximal tolerable dose (MTD)) showed effective anti-tumor activity (tumor growth inhibition rate (IR)=70.3%) against Li-7 (human liver cancer) xenografts transplanted into the peritoneal cavity. This procedure also resulted in increased life span (ILS (%)=47.2%), whereas CDDP dissolved in saline solution (CDDP-SOL) at a dose of 8 mg/kg (at MTD) was ineffective (IR=15.7%, ILS=2.6%). Likewise, CDDP-MS (35 mg/kg) significantly prolonged the mean survival time (ILS=50.8%) compared with a CDDP-SOL group (8 mg/kg) (ILS=13.1%) in the mice with Li-7 xenografts transplanted into the spleen. Furthermore, CDDP-MS showed markedly effective anti-tumor activity (IR=82.2%) against H-154 (human stomach cancer) xenografts, in which CDDP-SOL was effective (IR=69.5%) at the MTDs. The suppressive effect of CDDP-MS on accumulation of malignant ascites was intimately related to unchanged CDDP concentration in ascites. These results demonstrated that the administration of CDDP-MS resulted in an unchanged CDDP concentration in ascites, and induced a sustained tumor growth inhibition along with a prolonged survival time.
Tamura
Takashi
T
DDS Research Department, Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd., 16-89 Kashima 3-Chome, Yodogawa-ku, Osaka 532-8505, Japan. t-tamura@tanabe.co.jp
Fujita
Fumiko
F
Tanimoto
Masahiko
M
Koike
Masako
M
Suzuki
Akira
A
Fujita
Masahide
M
Horikiri
Yuji
Y
Sakamoto
Yasuo
Y
Suzuki
Takehiko
T
Yoshino
Hiroyuki
H
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity; D002945:Cisplatin / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008863:Microspheres; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured / Q000637:transplantation; D023041:Xenograft Model Antitumor Assays / Q000379:methods* / Q000706:statistics & numerical data
D000970:Antineoplastic Agents; D002945:Cisplatin