Journal
SURGERY TODAY
Volume 49, Issue 9, Pages 785-794Publisher
SPRINGER
DOI: 10.1007/s00595-019-01792-y
Keywords
Gelatin hydrogel; Peritoneal metastases; Intraperitoneal chemotherapy; Cisplatin; Gastric cancer
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Funding
- JSPS [JP15K08586]
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Purpose We previously reported the effectiveness of gelatin microspheres incorporating cisplatin in a mouse model of peritoneal metastases. In this study, we report our new complete sustained-release formula of gelatin hydrogel granules incorporating cisplatin (GHG-CDDP), which exerted a good anti-tumor effect with less toxicity. Methods GHG-CDDP was prepared without organic solvents to enable its future clinical use. The pharmaceutical characterization of GHG-CDDP was performed, and its in vivo degradability was evaluated. The anti-tumor effect was evaluated using a murine peritoneal metastasis model of the human gastric cancer MKN45-Luc cell line. Results Our new manufacturing process dramatically reduced the initial burst of CDDP release to approximately 2% (wt), while the previous product had a 25-30% initial burst. In intraperitoneal degradation tests, approximately 30% of GHG-CDDP remained in the murine abdominal cavity 7 days after intraperitoneal injection and disappeared within 3 weeks. GHG-CDDP significantly suppressed the in vivo tumor growth (p = 0.02) and prolonged the survival time (p = 0.0012) compared with the control. In contrast, free CDDP did not show a significant therapeutic effect at any dose. Weight loss and hematological toxicity were also significantly ameliorated. Conclusions GHG-CDDP is a promising treatment option for peritoneal metastases through the complete sustained-release of CDDP with less systemic toxicity.
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