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Intraperitoneal chemotherapy for peritoneal metastases using sustained release formula of cisplatin-incorporated gelatin hydrogel granules

  • Kota Yamashita
  • Shigeru TsunodaEmail author
  • Shutaro Gunji
  • Takahide Murakami
  • Takahisa Suzuki
  • Yasuhiko Tabata
  • Yoshiharu Sakai
Original Article
  • 26 Downloads

Abstract

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.

Keywords

Gelatin hydrogel Peritoneal metastases Intraperitoneal chemotherapy Cisplatin Gastric cancer 

Notes

Acknowledgements

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.

Author contributions

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.

Compliance with ethical standards

Conflict of interest

The authors confirm that they have no conflict of interest.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
  2. 2.Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Life and Medical SciencesKyoto UniversityKyotoJapan

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