Anti-tumor effect of intraperitoneal administration of cisplatin-loaded microspheres to human tumor xenografted nude mice
Autor: | Akira Suzuki, Hiroyuki Yoshino, Masahide Fujita, Masako Koike, Takashi Tamura, Fujita F, Takehiko Suzuki, Yuji Horikiri, Masahiko Tanimoto, Yasuo Sakamoto |
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Rok vydání: | 2002 |
Předmět: |
Male
inorganic chemicals Pathology medicine.medical_specialty Mice Nude Pharmaceutical Science Antineoplastic Agents Spleen Pharmacology Mice Peritoneal cavity Pharmacokinetics In vivo Ascites Tumor Cells Cultured Animals Humans Medicine neoplasms Peritoneal Neoplasms Cisplatin Mice Inbred BALB C business.industry Peritoneal fluid Xenograft Model Antitumor Assays Microspheres female genital diseases and pregnancy complications medicine.anatomical_structure Toxicity Female medicine.symptom business Injections Intraperitoneal Neoplasm Transplantation medicine.drug |
Zdroj: | Journal of Controlled Release. 80:295-307 |
ISSN: | 0168-3659 |
DOI: | 10.1016/s0168-3659(02)00003-2 |
Popis: | 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. |
Databáze: | OpenAIRE |
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