Intraperitoneal chemotherapy for peritoneal metastases using sustained release formula of cisplatin-incorporated gelatin hydrogel granules
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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.
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.
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.
GHG–CDDP is a promising treatment option for peritoneal metastases through the complete sustained-release of CDDP with less systemic toxicity.
KeywordsGelatin hydrogel Peritoneal metastases Intraperitoneal chemotherapy Cisplatin Gastric cancer
The authors would like to thank Dr. Takaki Sakurai for providing veterinary pathology opinions. This work was supported in part by a JSPS Grant-in-Aid for Scientific Research (C) Grant number JP15K08586.
KY, ST, YT, and YS designed the studies. KY, TM, and TS performed the experiments. KY and ST conducted the experiments and analyzed the data. SG assisted with the design of the experiments. KY and ST wrote the manuscript. YT and YS supervised and edited the manuscript. All authors contributed to the research.
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Conflict of interest
The authors confirm that they have no conflict of interest.
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